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[PMID]: 28466111 [Au] Autor: Angart PA; Carlson RJ; Thorwall S; Patrick Walton S [Ad] Endereço: Department of Chemical Engineering and Materials Science, Michigan State University, 428 S. Shaw Lane, Room 2100, Engineering Building, East Lansing, MI, 48824-1226, USA. [Ti] Título: Use of Brevibacillus choshinensis for the production of biologically active brain-derived neurotrophic factor (BDNF). [So] Source: Appl Microbiol Biotechnol;101(14):5645-5652, 2017 Jul. [Is] ISSN: 1432-0614 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family critical for neuronal cell survival and differentiation, with therapeutic potential for the treatment of neurological disorders and spinal cord injuries. The production of recombinant, bioactive BDNF is not practical in most traditional microbial expression systems because of the inability of the host to correctly form the characteristic cystine-knot fold of BDNF. Here, we investigated Brevibacillus choshinensis as a suitable expression host for bioactive BDNF expression, evaluating the effects of medium type (2SY and TM), temperature (25 and 30 °C), and culture time (48-120 h). Maximal BDNF bioactivity (per unit mass) was observed in cultures grown in 2SY medium at extended times (96 h at 30 °C or >72 h at 25 °C), with resulting bioactivity comparable to that of a commercially available BDNF. For cultures grown in 2SY medium at 25 °C for 72 h, the condition that led to the greatest quantity of biologically active protein in the shortest culture time, we recovered 264 µg/L of BDNF. As with other microbial expression systems, BDNF aggregates did form in all culture conditions, indicating that while we were able to recover biologically active BDNF, further optimization of the expression system could yield still greater quantities of bioactive protein. This study provides confirmation that B. choshinensis is capable of producing biologically active BDNF and that further optimization of culture conditions could prove valuable in increasing BDNF yields. [Mh] Termos MeSH primário: Fator Neurotrófico Derivado do Encéfalo/biossíntese Fator Neurotrófico Derivado do Encéfalo/farmacologia Brevibacillus/metabolismo [Mh] Termos MeSH secundário: Animais Fator Neurotrófico Derivado do Encéfalo/genética Fator Neurotrófico Derivado do Encéfalo/isolamento & purificação Brevibacillus/genética Proliferação Celular/efeitos dos fármacos Meios de Cultura/química Cistina/química Camundongos Células NIH 3T3 Neurônios/química Neurônios/metabolismo Proteínas Recombinantes/química Proteínas Recombinantes/genética Proteínas Recombinantes/isolamento & purificação Proteínas Recombinantes/metabolismo Temperatura Ambiente [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Brain-Derived Neurotrophic Factor); 0 (Culture Media); 0 (Recombinant Proteins); 48TCX9A1VT (Cystine) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180118 [Lr] Data última revisão: 180118 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170504 [St] Status: MEDLINE [do] DOI: 10.1007/s00253-017-8273-x

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[PMID]: 28747438 [Au] Autor: Seno K; Hayashi F [Ad] Endereço: From the Department of Biology, Faculty of Medicine, and. [Ti] Título: Palmitoylation is a prerequisite for dimerization-dependent raftophilicity of rhodopsin. [So] Source: J Biol Chem;292(37):15321-15328, 2017 09 15. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The visual photopigment rhodopsin (Rh) is a prototypical G protein-coupled receptor (GPCR) responsible for initiation of the phototransduction cascade in rod photoreceptors. Similar to other GPCRs, Rh can form dimers or even higher oligomers and tends to have a supramolecular organization that is likely important in the dim light response. Rh also exhibits high affinity for lipid rafts ( raftophilicity) upon light-dependent binding with the cognate G protein transducin (G ), suggesting the presence of lipid raft-like domains in the retinal disk membrane and their importance in phototransduction. However, the relationship between Rh oligomerization and lipid rafts in the disk membrane remains to be explored. Given previous findings that G binds to dimeric Rh and that Rh is posttranslationally modified with two highly raftophilic palmitoyl moieties, we hypothesized that Rh becomes raftophilic upon dimerization. Here, using biochemical assays, we found that Rh*-G complexes in the detergent-resistant membrane are partially resistant to cholesterol depletion by methyl-ß-cyclodextrin and that the Rh-to-G stoichiometry in this methyl-ß-cyclodextrin-resistant complex is 2:1. Next, we found that IgG-mediated Rh-Rh cross-linking renders Rh highly raftophilic, supporting the premise that Rh becomes raftophilic upon dimerization. Rh depalmitoylation via reduction of thioester linkages blocked the translocation of IgG-cross-linked Rh to the detergent-resistant membrane, highlighting that the two palmitoyl moieties are important for the dimerization-dependent raftophilicity of Rh. These results indicate that palmitoylated GPCRs such as Rh can acquire raftophilicity upon G protein-stabilized dimerization and thereby organize receptor-cluster rafts by recruiting raftophilic lipids. [Mh] Termos MeSH primário: Lipoilação Microdomínios da Membrana/metabolismo Modelos Moleculares Processamento de Proteína Pós-Traducional Rana catesbeiana/fisiologia Rodopsina/metabolismo Segmento Externo da Célula Bastonete/metabolismo [Mh] Termos MeSH secundário: Proteínas de Anfíbios/química Proteínas de Anfíbios/metabolismo Animais Anticorpos Monoclonais/metabolismo Cisteína/química Cistina/química Adaptação à Escuridão Dimerização Interações Hidrofóbicas e Hidrofílicas Cinética Luz Lipoilação/efeitos da radiação Microdomínios da Membrana/química Microdomínios da Membrana/efeitos da radiação Oxirredução Conformação Proteica/efeitos da radiação Multimerização Proteica/efeitos da radiação Processamento de Proteína Pós-Traducional/efeitos da radiação Estabilidade Proteica/efeitos da radiação Rodopsina/química Segmento Externo da Célula Bastonete/química Segmento Externo da Célula Bastonete/efeitos da radiação Transducina/química Transducina/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Amphibian Proteins); 0 (Antibodies, Monoclonal); 48TCX9A1VT (Cystine); 9009-81-8 (Rhodopsin); EC 3.6.5.1 (Transducin); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171230 [Lr] Data última revisão: 171230 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170728 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.804880

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[PMID]: 28771427 [Au] Autor: Schwarz E [Ad] Endereço: . [Ti] Título: Cystine knot growth factors and their functionally versatile proregions. [So] Source: Biol Chem;398(12):1295-1308, 2017 Nov 27. [Is] ISSN: 1437-4315 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: The cystine knot disulfide pattern has been found to be widespread in nature, since it has been detected in proteins from plants, marine snails, spiders and mammals. Cystine knot proteins are secreted proteins. Their functions range from defense mechanisms as toxins, e.g. ion channel or enzyme inhibitors, to hormones, blood factors and growth factors. Cystine knot proteins can be divided into two superordinate groups. (i) The cystine knot peptides, also referred to - with other non-cystine knot proteins - as knottins, with linear and cyclic polypeptide chains. (ii) The cystine knot growth factor family, which is in the focus of this article. The disulfide ring structure of the cystine knot peptides is made up by the half-cystines 1-4 and 2-5, and the threading disulfide bond is formed by the half-cystines, 3-6. In the growth factor group, the disulfides of half-cystines 1 and 4 pass the ring structure formed by the half-cystines 2-5 and 3-6. In this review, special emphasis will be devoted to the growth factor cystine knot proteins and their proregions. The latter have shifted into the focus of scientific interest as their important biological roles are just to be unravelled. [Mh] Termos MeSH primário: Cistina/metabolismo Peptídeos e Proteínas de Sinalização Intercelular/química Peptídeos e Proteínas de Sinalização Intercelular/metabolismo [Mh] Termos MeSH secundário: Animais Seres Humanos Conformação Proteica [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Intercellular Signaling Peptides and Proteins); 48TCX9A1VT (Cystine) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171113 [Lr] Data última revisão: 171113 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170804 [St] Status: MEDLINE

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[PMID]: 28751379 [Au] Autor: Jansson AM; Csiszar A; Maier J; Nyström AC; Ax E; Johansson P; Schiavone LH [Ad] Endereço: From the Reagents and Assay Development Division, Discovery Sciences Department. [Ti] Título: The interleukin-like epithelial-mesenchymal transition inducer ILEI exhibits a non-interleukin-like fold and is active as a domain-swapped dimer. [So] Source: J Biol Chem;292(37):15501-15511, 2017 Sep 15. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Production and secretion of pro-metastatic proteins is a feature of many tumor cells. The FAM3C interleukin-like epithelial-to-mesenchymal-transition (EMT) inducer (ILEI) has been shown to be strongly up-regulated in several cancers and to be essential for tumor formation and metastasis in epithelial cells, correlating with a significant decrease in overall survival in colon and breast cancer patients. ILEI has been seen to interact with the γ-secretase presenilin 1 subunit (PS1). However, not much is known about the mechanism-of-action or the detailed ILEI structure. We present here the crystal structures of FAM3C ILEI and show that it exists as monomers but also as covalent dimers. The observed ILEI ß-ß-α fold confirmed previous indications that the FAM3C proteins do not form classical four-helix-bundle structures as was initially predicted. This provides the first experimental evidence that the interleukin-like EMT inducers are not evolutionarily related to the interleukins. However, more surprisingly, the ILEI dimer structure was found to feature a -linked domain swap, converting an intramolecular disulfide to intermolecular. Interestingly, dimeric but not monomeric ILEI was subsequently found to cause a dose-dependent increase in EpRas cell invasiveness comparable with TGF-ß, indicating that the dimer might be the active ILEI species. This is in line with a parallel study showing that covalent oligomerization of ILEI is essential for EMT and tumor progression The structures and the activity data give some first insight into the relationship between dimerization and ILEI function as well as indicate an intriguing link between ILEI, the PS1-protease, TGF-ß, and the TGF-ß receptor 1. [Mh] Termos MeSH primário: Citocinas/metabolismo Modelos Moleculares Proteínas de Neoplasias/metabolismo [Mh] Termos MeSH secundário: Substituição de Aminoácidos Animais Linhagem Celular Transformada Movimento Celular Cristalografia por Raios X Cisteína/química Cistina/química Citocinas/química Citocinas/genética Dimerização Seres Humanos Interleucinas/química Interleucinas/metabolismo Camundongos Proteínas de Neoplasias/química Proteínas de Neoplasias/genética Fragmentos de Peptídeos/química Fragmentos de Peptídeos/genética Fragmentos de Peptídeos/metabolismo Mutação Puntual Conformação Proteica Domínios e Motivos de Interação entre Proteínas Estabilidade Proteica Proteínas Recombinantes de Fusão/química Proteínas Recombinantes de Fusão/metabolismo Homologia Estrutural de Proteína [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cytokines); 0 (FAM3C protein, human); 0 (Fam3c protein, mouse); 0 (Interleukins); 0 (Neoplasm Proteins); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 48TCX9A1VT (Cystine); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170927 [Lr] Data última revisão: 170927 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170729 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.782904

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[PMID]: 28739872 [Au] Autor: Bassi R; Burgoyne JR; DeNicola GF; Rudyk O; DeSantis V; Charles RL; Eaton P; Marber MS [Ad] Endereço: From the King's College London British Heart Foundation Centre of Excellence, Department of Cardiology, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom. [Ti] Título: Redox-dependent dimerization of p38α mitogen-activated protein kinase with mitogen-activated protein kinase kinase 3. [So] Source: J Biol Chem;292(39):16161-16173, 2017 Sep 29. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The kinase p38α MAPK (p38α) plays a pivotal role in many biological processes. p38α is activated by canonical upstream kinases that phosphorylate the activation region. The purpose of our study was to determine whether such activation may depend on redox-sensing cysteines within p38α. p38α was activated and formed a disulfide-bound heterodimer with MAP2K3 (MKK3) in rat cardiomyocytes and isolated hearts exposed to H O This disulfide heterodimer was sensitive to reduction by mercaptoethanol and was enhanced by the thioredoxin-reductase inhibitor auranofin. We predicted that Cys-119 or Cys-162 of p38α, close to the known MKK3 docking domain, were relevant for these redox characteristics. The C119S mutation decreased whereas the C162S mutation increased the dimer formation, suggesting that these two Cys residues act as vicinal thiols, consistent with C119S/C162S being incapable of sensing H O Similarly, disulfide heterodimer formation was abolished in H9C2 cells expressing both MKK3 and p38α C119S/C162S and subjected to simulated ischemia and reperfusion. However, the p38α C119S/C162S mutants did not exhibit appreciable alteration in activating dual phosphorylation. In contrast, the anti-inflammatory agent 10-nitro-oleic acid (NO -OA), a component of the Mediterranean diet, reduced p38α activation and covalently modified Cys-119/Cys-162, probably obstructing MKK3 access. Moreover, NO -OA reduced the dephosphorylation of p38α by hematopoietic tyrosine phosphatase (HePTP). Furthermore, steric obstruction of Cys-119/Cys-162 by NO -OA pretreatment in Langendorff-perfused murine hearts prevented the p38-MKK3 disulfide dimer formation and attenuated H O -induced contractile dysfunction. Our findings suggest that cysteine residues within p38α act as redox sensors that can dynamically regulate the association between p38 and MKK3. [Mh] Termos MeSH primário: Cistina/metabolismo Ventrículos do Coração/enzimologia MAP Quinase Quinase 3/metabolismo Proteína Quinase 14 Ativada por Mitógeno/metabolismo Modelos Moleculares Miócitos Cardíacos/enzimologia Estresse Oxidativo [Mh] Termos MeSH secundário: Substituição de Aminoácidos Animais Linhagem Celular Células Cultivadas Cisteína/química Cisteína/metabolismo Cistina/química Ativação Enzimática Ventrículos do Coração/citologia Ventrículos do Coração/metabolismo Seres Humanos Técnicas In Vitro MAP Quinase Quinase 3/química MAP Quinase Quinase 3/genética Masculino Camundongos Endogâmicos C57BL Proteína Quinase 14 Ativada por Mitógeno/química Proteína Quinase 14 Ativada por Mitógeno/genética Miócitos Cardíacos/citologia Miócitos Cardíacos/metabolismo Oxirredução Conformação Proteica Multimerização Proteica Ratos Wistar Proteínas Recombinantes de Fusão/química Proteínas Recombinantes de Fusão/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Recombinant Fusion Proteins); 48TCX9A1VT (Cystine); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14); EC 2.7.12.2 (MAP Kinase Kinase 3); EC 2.7.12.2 (Map2k3 protein, rat); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170726 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.785410

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[PMID]: 28739804 [Au] Autor: Pilipczuk J; Zalewska-Piatek B; Bruzdziak P; Czub J; Wieczór M; Olszewski M; Wanarska M; Nowicki B; Augustin-Nowacka D; Piatek R [Ad] Endereço: From the Departments of Molecular Biotechnology and Microbiology and. [Ti] Título: Role of the disulfide bond in stabilizing and folding of the fimbrial protein DraE from uropathogenic . [So] Source: J Biol Chem;292(39):16136-16149, 2017 Sep 29. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Dr fimbriae are homopolymeric adhesive organelles of uropathogenic composed of DraE subunits, responsible for the attachment to host cells. These structures are characterized by enormously high stability resulting from the structural properties of an Ig-like fold of DraE. One feature of DraE and other fimbrial subunits that makes them peculiar among Ig-like domain-containing proteins is a conserved disulfide bond that joins their A and B strands. Here, we investigated how this disulfide bond affects the stability and folding/unfolding pathway of DraE. We found that the disulfide bond stabilizes self-complemented DraE (DraE-sc) by ∼50 kJ mol in an exclusively thermodynamic manner, by lowering the free energy of the native state and with almost no effect on the free energy of the transition state. This finding was confirmed by experimentally determined folding and unfolding rate constants of DraE-sc and a disulfide bond-lacking DraE-sc variant. Although the folding of both proteins exhibited similar kinetics, the unfolding rate constant changed upon deletion of the disulfide bond by 10 orders of magnitude, from ∼10 s to 10 s Molecular simulations revealed that unfolding of the disulfide bond-lacking variant is initiated by strands A or G and that disulfide bond-mediated joining of strand A to the core strand B cooperatively stabilizes the whole protein. We also show that the disulfide bond in DraE is recognized by the DraB chaperone, indicating a mechanism that precludes the incorporation of less stable, non-oxidized DraE forms into the fimbriae. [Mh] Termos MeSH primário: Adesinas Bacterianas/metabolismo Cistina/química Proteínas de Escherichia coli/metabolismo Proteínas de Fímbrias/metabolismo Modelos Moleculares Escherichia coli Uropatogênica/fisiologia [Mh] Termos MeSH secundário: Adesinas Bacterianas/química Adesinas Bacterianas/genética Sequência de Aminoácidos Substituição de Aminoácidos Aderência Bacteriana Linhagem Celular Tumoral Sequência Conservada Cisteína/química Transferência de Energia Proteínas de Escherichia coli/química Proteínas de Escherichia coli/genética Proteínas de Fímbrias/química Proteínas de Fímbrias/genética Seres Humanos Cinética Simulação de Dinâmica Molecular Mutação Oxirredução Conformação Proteica Dobramento de Proteína Redobramento de Proteína Estabilidade Proteica Proteínas Recombinantes/química Proteínas Recombinantes/metabolismo [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Adhesins, Bacterial); 0 (DraE protein, E coli); 0 (Escherichia coli Proteins); 0 (Recombinant Proteins); 147680-16-8 (Fimbriae Proteins); 48TCX9A1VT (Cystine); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170726 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.785477

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[PMID]: 28739132 [Au] Autor: Liu L; Wang X; Yang J; Bai Y [Ad] Endereço: Chemistry Department, Jinan University, Guangzhou 510632, PR China. [Ti] Título: Colorimetric sensing of selenocystine using gold nanoparticles. [So] Source: Anal Biochem;535:19-24, 2017 Oct 15. [Is] ISSN: 1096-0309 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: We present a highly selective and sensitive colorimetric method for the detection of selenocystine (SeCys) coexisting with other amino acids, especially cysteine (Cys) using the gold nanoparticles (AuNPs). Firstly, Cys was oxidized to cystine (Cys-Cys) by dissolved oxygen under Cu catalysis in the pre-reaction, which eliminated the interference of Cys in the SeCys sensing process. Then SeCys induced the rapid aggregation of AuNPs through Au-Se bond and complex formation of Cu -SeCys in the colorimetric reaction, in which the color change of AuNPs from red to blue or purple with the naked eye detection or with a UV-vis spectrophotometric determination. The concentration of SeCys was quantified by the value at 670 nm from the second-derivative SPR absorbance spectrum. The linear range was from 2 µM to 14 µM with correlation coefficient of 0.999 and a detection limit (LOD) was 0.14 µM. Moreover, the colorimetric response of AuNPs exhibited remarkable specificity to SeCys coexisting with 18 amino acids in a simulation sample, in which the total concentration of Cys and Cys-Cys was less than 15 µM and the each concentration of other 16 common amino acids was 10 µM. [Mh] Termos MeSH primário: Colorimetria Cistina/análogos & derivados Ouro/química Nanopartículas Metálicas/química Compostos Organosselênicos/análise [Mh] Termos MeSH secundário: Cistina/análise Estrutura Molecular [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Organoselenium Compounds); 1464-43-3 (selenocystine); 48TCX9A1VT (Cystine); 7440-57-5 (Gold) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170922 [Lr] Data última revisão: 170922 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170726 [St] Status: MEDLINE

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[PMID]: 28655768 [Au] Autor: Asciolla JJ; Miele MM; Hendrickson RC; Resh MD [Ad] Endereço: From the Cell Biology Program and. [Ti] Título: An fatty acylation assay reveals a mechanism for Wnt recognition by the acyltransferase Porcupine. [So] Source: J Biol Chem;292(33):13507-13513, 2017 Aug 18. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Wnt proteins are a family of secreted signaling proteins that play key roles in regulating cell proliferation in both embryonic and adult tissues. Production of active Wnt depends on attachment of palmitoleate, a monounsaturated fatty acid, to a conserved serine by the acyltransferase Porcupine (PORCN). Studies of PORCN activity relied on cell-based fatty acylation and signaling assays as no direct enzyme assay had yet been developed. Here, we present the first assay that accurately recapitulates PORCN-mediated fatty acylation of a Wnt substrate. The critical feature is the use of a double disulfide-bonded Wnt peptide that mimics the two-dimensional structure surrounding the Wnt acylation site. PORCN-mediated Wnt acylation was abolished when the Wnt peptide was treated with DTT, and did not occur with a linear (non-disulfide-bonded) peptide, or when the double disulfide-bonded Wnt peptide contained Ala substituted for the Ser acylation site. We exploited this Wnt acylation assay to provide direct evidence that the small molecule LGK974, which is in clinical trials for managing Wnt-driven tumors, is a PORCN inhibitor whose IC for inhibition of Wnt fatty acylation closely matches that for inhibition of Wnt signaling. Side-by-side comparison of PORCN and Hedgehog acyltransferase (HHAT), two enzymes that attach 16-carbon fatty acids to secreted proteins, revealed that neither enzyme will accept the other's fatty acyl-CoA or peptide substrates. These findings illustrate the unique enzyme-substrate selectivity exhibited by members of the membrane-bound -acyl transferase family. [Mh] Termos MeSH primário: Aciltransferases/metabolismo Hipoplasia Dérmica Focal/genética Proteínas de Membrana/metabolismo Mutação Puntual Processamento de Proteína Pós-Traducional Proteína Wnt3A/metabolismo [Mh] Termos MeSH secundário: Acilação/efeitos dos fármacos Aciltransferases/antagonistas & inibidores Aciltransferases/química Aciltransferases/genética Substituição de Aminoácidos Animais Cistina/química Cistina/metabolismo Inibidores Enzimáticos/farmacologia Hipoplasia Dérmica Focal/metabolismo Células HEK293 Seres Humanos Proteínas de Membrana/antagonistas & inibidores Proteínas de Membrana/química Proteínas de Membrana/genética Camundongos Mutagênese Sítio-Dirigida Fragmentos de Peptídeos/química Fragmentos de Peptídeos/metabolismo Conformação Proteica Processamento de Proteína Pós-Traducional/efeitos dos fármacos Proteínas Recombinantes de Fusão/química Proteínas Recombinantes de Fusão/metabolismo Especificidade por Substrato Via de Sinalização Wnt/efeitos dos fármacos Proteína Wnt3A/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Enzyme Inhibitors); 0 (Membrane Proteins); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (WNT3A protein, human); 0 (Wnt3A Protein); 48TCX9A1VT (Cystine); EC 2.3.- (Acyltransferases); EC 2.3.1.- (HHAT protein, human); EC 2.3.1.- (PORCN protein, human); EC 2.3.1.- (Porcn protein, mouse) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171115 [Lr] Data última revisão: 171115 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170629 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.C117.800136

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[PMID]: 28655765 [Au] Autor: Shimizu H; Tosaki A; Ohsawa N; Ishizuka-Katsura Y; Shoji S; Miyazaki H; Oyama F; Terada T; Shirouzu M; Sekine SI; Nukina N; Yokoyama S [Ad] Endereço: From the RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan. [Ti] Título: Parallel homodimer structures of the extracellular domains of the voltage-gated sodium channel ß4 subunit explain its role in cell-cell adhesion. [So] Source: J Biol Chem;292(32):13428-13440, 2017 Aug 11. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Voltage-gated sodium channels (VGSCs) are transmembrane proteins required for the generation of action potentials in excitable cells and essential for propagating electrical impulses along nerve cells. VGSCs are complexes of a pore-forming α subunit and auxiliary ß subunits, designated as ß1/ß1B-ß4 (encoded by respectively), which also function in cell-cell adhesion. We previously reported the structural basis for the homophilic interaction of the ß4 subunit, which contributes to its adhesive function. Here, using crystallographic and biochemical analyses, we show that the ß4 extracellular domains directly interact with each other in a parallel manner that involves an intermolecular disulfide bond between the unpaired Cys residues (Cys ) in the loop connecting strands B and C and intermolecular hydrophobic and hydrogen-bonding interactions of the N-terminal segments (Ser -Val ). Under reducing conditions, an N-terminally deleted ß4 mutant exhibited decreased cell adhesion compared with the wild type, indicating that the ß4 dimer contributes to the homophilic interaction of ß4 in cell-cell adhesion. Furthermore, this mutant exhibited increased association with the α subunit, indicating that the dimerization of ß4 affects α-ß4 complex formation. These observations provide the structural basis for the parallel dimer formation of ß4 in VGSCs and reveal its mechanism in cell-cell adhesion. [Mh] Termos MeSH primário: Modelos Moleculares Subunidade beta-4 do Canal de Sódio Disparado por Voltagem/metabolismo [Mh] Termos MeSH secundário: Animais Células CHO Adesão Celular Cricetulus Cristalografia por Raios X Cisteína/química Cistina/química Dimerização Seres Humanos Ligações de Hidrogênio Interações Hidrofóbicas e Hidrofílicas Camundongos Fragmentos de Peptídeos/química Fragmentos de Peptídeos/genética Fragmentos de Peptídeos/metabolismo Conformação Proteica Conformação Proteica em Folha beta Domínios e Motivos de Interação entre Proteínas Multimerização Proteica Proteínas Recombinantes de Fusão/química Proteínas Recombinantes de Fusão/metabolismo Proteínas Recombinantes/química Proteínas Recombinantes/metabolismo Subunidade beta-4 do Canal de Sódio Disparado por Voltagem/química Subunidade beta-4 do Canal de Sódio Disparado por Voltagem/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (SCN4B protein, human); 0 (Scn4b protein, mouse); 0 (Voltage-Gated Sodium Channel beta-4 Subunit); 48TCX9A1VT (Cystine); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170825 [Lr] Data última revisão: 170825 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170629 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.786509

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MEDLINE

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[PMID]: 28642371 [Au] Autor: Houot L; Navarro R; Nouailler M; Duché D; Guerlesquin F; Lloubes R [Ad] Endereço: From the Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UMR7255, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université-CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France lhouot@imm.cnrs.fr. [Ti] Título: Electrostatic interactions between the CTX phage minor coat protein and the bacterial host receptor TolA drive the pathogenic conversion of . [So] Source: J Biol Chem;292(33):13584-13598, 2017 Aug 18. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: is a natural inhabitant of aquatic environments and converts to a pathogen upon infection by a filamentous phage, CTXΦ, that transmits the cholera toxin-encoding genes. This toxigenic conversion of has evident implication in both genome plasticity and epidemic risk, but the early stages of the infection have not been thoroughly studied. CTXΦ transit across the bacterial periplasm requires binding between the minor coat protein named pIII and a bacterial inner-membrane receptor, TolA, which is part of the conserved Tol-Pal molecular motor. To gain insight into the TolA-pIII complex, we developed a bacterial two-hybrid approach, named Oxi-BTH, suited for studying the interactions between disulfide bond-folded proteins in the bacterial cytoplasm of an reporter strain. We found that two of the four disulfide bonds of pIII are required for its interaction with TolA. By combining Oxi-BTH assays, NMR, and genetic studies, we also demonstrate that two intermolecular salt bridges between TolA and pIII provide the driving forces of the complex interaction. Moreover, we show that TolA residue Arg-325 involved in one of the two salt bridges is critical for proper functioning of the Tol-Pal system. Our results imply that to prevent host evasion, CTXΦ uses an infection strategy that targets a highly conserved protein of Gram-negative bacteria essential for the fitness of in its natural environment. [Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo Bacteriófagos/fisiologia Proteínas do Capsídeo/metabolismo Modelos Moleculares Receptores Virais/metabolismo Vibrio cholerae/metabolismo [Mh] Termos MeSH secundário: Substituição de Aminoácidos Arginina/química Proteínas de Bactérias/química Proteínas de Bactérias/genética Sítios de Ligação Proteínas do Capsídeo/química Proteínas do Capsídeo/genética Cristalografia por Raios X Cistina/química Deleção de Genes Mutagênese Sítio-Dirigida Mutação Puntual Conformação Proteica Domínios e Motivos de Interação entre Proteínas Multimerização Proteica Receptores Virais/química Receptores Virais/genética Proteínas Recombinantes de Fusão/química Proteínas Recombinantes de Fusão/metabolismo Proteínas Recombinantes/química Proteínas Recombinantes/metabolismo Eletricidade Estática Homologia Estrutural de Proteína Técnicas do Sistema de Duplo-Híbrido Vibrio cholerae/patogenicidade Vibrio cholerae/virologia Tropismo Viral [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Capsid Proteins); 0 (Receptors, Virus); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 48TCX9A1VT (Cystine); 94ZLA3W45F (Arginine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170906 [Lr] Data última revisão: 170906 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170624 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.786061

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