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Pesquisa : D12.776.124.486.274.850 [Categoria DeCS]
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[PMID]:28578024
[Au] Autor:Taylor RP; Lindorfer MA; Cook EM; Beurskens FJ; Schuurman J; Parren PWHI; Zent CS; VanDerMeid KR; Burack R; Mizuno M; Morgan BP
[Ad] Endereço:Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, USA. Electronic address: rpt@eservices.virginia.edu.
[Ti] Título:Hexamerization-enhanced CD20 antibody mediates complement-dependent cytotoxicity in serum genetically deficient in C9.
[So] Source:Clin Immunol;181:24-28, 2017 Aug.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca during CDC (as assessed with FLUO-4) that were extended in time. This suggests that small C5b-8 pores allow Ca to enter the cell, while dissipation of the fluorescent signal accompanying cell disintegration is delayed. The Ca signal is retained concomitantly with TOPRO-3 (viability dye) staining, thereby confirming that Ca influx represents the most proximate mediator of cell death by CDC.
[Mh] Termos MeSH primário: Complemento C9/deficiência
Proteínas do Sistema Complemento/imunologia
Síndromes de Imunodeficiência/imunologia
Leucemia Linfocítica Crônica de Células B
Rituximab/farmacologia
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Complemento C9/imunologia
Complexo de Ataque à Membrana do Sistema Complemento/imunologia
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo
Proteínas do Sistema Complemento/metabolismo
Seres Humanos
Imunoterapia
Polimerização
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C9); 0 (Complement Membrane Attack Complex); 0 (complement C5b-8 complex); 4F4X42SYQ6 (Rituximab); 9007-36-7 (Complement System Proteins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170605
[St] Status:MEDLINE


  2 / 765 MEDLINE  
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[PMID]:28150868
[Au] Autor:Prasada RT; Lakshmi PT; Parvathy R; Murugavel S; Karuna D; Paritosh J
[Ad] Endereço:Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar 243122, Uttar Pradesh, India.
[Ti] Título:Identification of second arginine-glycine-aspartic acid motif of ovine vitronectin as the complement C9 binding site and its implication in bacterial infection.
[So] Source:Microbiol Immunol;61(2):75-84, 2017 Feb.
[Is] ISSN:1348-0421
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Vitronectin (Vn), a multifunctional protein of blood and extracellular matrix, interacts with complement C9. This interaction may modulate innate immunity. Details of Vn-C9 interactions are limited. Vn-C9 interactions were assessed by employing a goat homologous system and observing Vn binding to C9 in three different assays. Using recombinant fragments, C9 binding was mapped to the N-terminus of Vn. Site directed mutagenesis was performed to alter the second arginine glycine aspartic acid (RGD) sequence (RGD-2) of Vn. Changing R to G or D to A in RGD-2 caused significant decrease in Vn binding to C9 whereas changing of R to G in the first RGD motif (RGD-1) had no effect on Vn binding to C9. These results imply that the RGD-2 of goat Vn is involved in C9 binding. In a competitive binding assay, the presence of soluble RGD peptide inhibited Vn binding to C9 whereas heparin had no effect. Vn binding to C9 was also evaluated in terms of bacterial pathogenesis. Serum dependent inhibition of Escherichia coli growth was significantly reverted when Vn or its N-fragment were included in the assay. The C-fragment, which did not support C9 binding, also partly nullified serum-dependent inhibition of bacterial growth, probably through other serum component(s).
[Mh] Termos MeSH primário: Motivos de Aminoácidos
Complemento C9/metabolismo
Fatores Imunológicos/metabolismo
Vitronectina/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Atividade Bactericida do Sangue
Complemento C9/imunologia
Análise Mutacional de DNA
Escherichia coli/imunologia
Cabras
Fatores Imunológicos/imunologia
Mutagênese Sítio-Dirigida
Ligação Proteica
Vitronectina/genética
Vitronectina/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C9); 0 (Immunologic Factors); 0 (Vitronectin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170418
[Lr] Data última revisão:
170418
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE
[do] DOI:10.1111/1348-0421.12468


  3 / 765 MEDLINE  
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[PMID]:27474078
[Au] Autor:Cook EM; Lindorfer MA; van der Horst H; Oostindie S; Beurskens FJ; Schuurman J; Zent CS; Burack R; Parren PW; Taylor RP
[Ad] Endereço:Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908;
[Ti] Título:Antibodies That Efficiently Form Hexamers upon Antigen Binding Can Induce Complement-Dependent Cytotoxicity under Complement-Limiting Conditions.
[So] Source:J Immunol;197(5):1762-75, 2016 Sep 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently, we demonstrated that IgG Abs can organize into ordered hexamers after binding their cognate Ags expressed on cell surfaces. This process is dependent on Fc:Fc interactions, which promote C1q binding, the first step in classical pathway complement activation. We went on to engineer point mutations that stimulated IgG hexamer formation and complement-dependent cytotoxicity (CDC). The hexamer formation-enhanced (HexaBody) CD20 and CD38 mAbs support faster, more robust CDC than their wild-type counterparts. To further investigate the CDC potential of these mAbs, we used flow cytometry, high-resolution digital imaging, and four-color confocal microscopy to examine their activity against B cell lines and primary chronic lymphocytic leukemia cells in sera depleted of single complement components. We also examined the CDC activity of alemtuzumab (anti-CD52) and mAb W6/32 (anti-HLA), which bind at high density to cells and promote substantial complement activation. Although we observed little CDC for mAb-opsonized cells reacted with sera depleted of early complement components, we were surprised to discover that the Hexabody mAbs, as well as ALM and W6/32, were all quite effective at promoting CDC in sera depleted of individual complement components C6 to C9. However, neutralization studies conducted with an anti-C9 mAb verified that C9 is required for CDC activity against cell lines. These highly effective complement-activating mAbs efficiently focus activated complement components on the cell, including C3b and C9, and promote CDC with a very low threshold of MAC binding, thus providing additional insight into their enhanced efficacy in promoting CDC.
[Mh] Termos MeSH primário: ADP-Ribosil Ciclase 1/metabolismo
Anticorpos Monoclonais/química
Anticorpos Monoclonais/imunologia
Citotoxicidade Celular Dependente de Anticorpos
Antígenos CD20/metabolismo
Antígenos/imunologia
Sítios de Ligação de Anticorpos
Complemento C9/metabolismo
Glicoproteínas de Membrana/metabolismo
[Mh] Termos MeSH secundário: ADP-Ribosil Ciclase 1/imunologia
Alemtuzumab
Anticorpos Monoclonais Humanizados/imunologia
Antígenos CD20/imunologia
Linfócitos B/imunologia
Linhagem Celular Tumoral
Ativação do Complemento
Complemento C3b/metabolismo
Complemento C9/imunologia
Proteínas do Sistema Complemento/imunologia
Proteínas do Sistema Complemento/metabolismo
Seres Humanos
Glicoproteínas de Membrana/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Monoclonal, Humanized); 0 (Antigens); 0 (Antigens, CD20); 0 (Complement C9); 0 (Membrane Glycoproteins); 3A189DH42V (Alemtuzumab); 80295-43-8 (Complement C3b); 9007-36-7 (Complement System Proteins); EC 3.2.2.5 (CD38 protein, human); EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160731
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600648


  4 / 765 MEDLINE  
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[PMID]:27337595
[Au] Autor:Kotimaa J; Klar-Mohammad N; Gueler F; Schilders G; Jansen A; Rutjes H; Daha MR; van Kooten C
[Ad] Endereço:Leiden University Medical Center (LUMC), Department of Nephrology, Leiden, The Netherlands.
[Ti] Título:Sex matters: Systemic complement activity of female C57BL/6J and BALB/cJ mice is limited by serum terminal pathway components.
[So] Source:Mol Immunol;76:13-21, 2016 08.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Experimental mouse models have been extensively used to elucidate the role of the complement system in different diseases and injuries. Contribution of gender has revealed an intriguing gender specific difference; female mice often show protection against most complement driven injuries such as ischemia/reperfusion injury, graft rejection and sepsis. Interestingly, early studies to the mouse complement system revealed that female mice have very low total complement activity (CH50), which is related to androgen regulation of hepatic complement synthesis. Here, our aim was to understand at which level the female specific differences in mouse complement resides. We have used recently developed complement assays to study the functional activities of female and male mice at the level of C3 and C9 activation, and furthermore assayed key complement factor levels in serum of age-matched female and male C57BL/6 mice. Our results show that the female mice have normal complement cascade functionality at the level of C3 activation, which was supported by determinations of early complement factors. However, all pathways are strongly reduced at the level of C9 activation, suggesting a terminal pathway specific difference. This was in line with C6 and C9 measurements, showing strongly decreased levels in females. Furthermore, similar gender differences were also found in BALB/cJ mice, but not in CD-1 mice. Our results clearly demonstrate that the complement system in females of frequently used mouse strains is restricted by the terminal pathway components and that the perceived female specific protection against experimental disease and injury might be in part explained by the inability promote inflammation through C5b-9.
[Mh] Termos MeSH primário: Ativação do Complemento/imunologia
Complemento C3/imunologia
Complemento C6/imunologia
Complemento C9/imunologia
Caracteres Sexuais
[Mh] Termos MeSH secundário: Animais
Western Blotting
Ensaio de Imunoadsorção Enzimática
Feminino
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Complement C3); 0 (Complement C6); 0 (Complement C9)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160624
[St] Status:MEDLINE


  5 / 765 MEDLINE  
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[PMID]:27077104
[Au] Autor:Leung LL; Morser J
[Ad] Endereço:Stanford University School of Medicine, Division of Hematology, Stanford, CA 94305, USA.
[Ti] Título:Plasmin as a complement C5 convertase.
[So] Source:EBioMedicine;5:20-1, 2016 Mar.
[Is] ISSN:2352-3964
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Mh] Termos MeSH primário: Convertases de Complemento C3-C5
Fibrinolisina
[Mh] Termos MeSH secundário: Enzimas Ativadoras do Complemento
Ativação do Complemento
Complemento C2
Complemento C3
Complemento C3b
Complemento C4
Complemento C5
Complemento C6
Complemento C9
Via Alternativa do Complemento
Seres Humanos
[Pt] Tipo de publicação:COMMENT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C2); 0 (Complement C3); 0 (Complement C4); 0 (Complement C5); 0 (Complement C6); 0 (Complement C9); 80295-43-8 (Complement C3b); EC 3.- (Complement Activating Enzymes); EC 3.4.21.- (Complement C3-C5 Convertases); EC 3.4.21.7 (Fibrinolysin)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160416
[Lr] Data última revisão:
160416
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160415
[St] Status:MEDLINE
[do] DOI:10.1016/j.ebiom.2016.03.015


  6 / 765 MEDLINE  
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[PMID]:27005612
[Au] Autor:Zheng H; Ji W; Zhang GR; Zhang XT; Shi ZC; Wei KJ; Yang RB; Gardner JP
[Ad] Endereço:Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China. zhenghyt@126.com.
[Ti] Título:Molecular Characterization and Expression Analyses of the Complement Component C8α, C8ß and C9 Genes in Yellow Catfish (Pelteobagrus fulvidraco) after the Aeromonas hydrophila Challenge.
[So] Source:Int J Mol Sci;17(3):345, 2016 Mar 08.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The complement components C8α, C8ß and C9 have important roles in the innate immune system against invading microorganisms. Partial cDNA sequences of the Pf_C8α, Pf_C8ß and Pf_C9 genes (Pf: abbreviation of Pelteobagrus fulvidraco) were cloned from yellow catfish. The Pf_C8α, Pf_C8ß and Pf_C9 genes showed the greatest amino acid similarity to C8α (54%) and C8ß (62%) of zebrafish and to C9 (52%) of grass carp, respectively. Ontogenetic expression analyses using real-time quantitative PCR suggested that the three genes may play crucial roles during embryonic and early larval development. The mRNA expressions of the three genes were all at the highest levels in liver tissue, and at lower or much lower levels in 16 other tissues, demonstrating that the liver is the primary site for the protein synthesis of Pf_C8α, Pf_C8ß and Pf_C9. Injection of Aeromonas hydrophila led to up-regulation of the three genes in the spleen, head kidney, kidney, liver and blood tissues, indicating that the three genes may contribute to the host's defense against invading pathogenic microbes. An increased understanding of the functions of the Pf_C8α, Pf_C8ß and Pf_C9 genes in the innate immunity of yellow catfish will help enhance production of this valuable freshwater species.
[Mh] Termos MeSH primário: Aeromonas hydrophila
Peixes-Gato/imunologia
Complemento C8/genética
Complemento C9/genética
Proteínas de Peixes/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência de Bases
Peixes-Gato/genética
Peixes-Gato/microbiologia
Doenças dos Peixes/microbiologia
Regulação da Expressão Gênica
Infecções por Bactérias Gram-Negativas/imunologia
Infecções por Bactérias Gram-Negativas/veterinária
Especificidade de Órgãos
Filogenia
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Complement C8); 0 (Complement C9); 0 (Fish Proteins)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170116
[Lr] Data última revisão:
170116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160324
[St] Status:MEDLINE


  7 / 765 MEDLINE  
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[PMID]:26940098
[Au] Autor:Salih M; Demmers JA; Bezstarosti K; Leonhard WN; Losekoot M; van Kooten C; Gansevoort RT; Peters DJ; Zietse R; Hoorn EJ; DIPAK Consortium
[Ad] Endereço:Department of Internal Medicine, Division of Nephrology & Transplantation, and.
[Ti] Título:Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney Disease.
[So] Source:J Am Soc Nephrol;27(10):3079-3092, 2016 Oct.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Novel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs from healthy controls and patients with ADPKD using a labeled approach and then used a label-free approach with uEVs of different subjects (healthy controls versus patients with ADPKD versus patients with non-ADPKD CKD). In both experiments, 30 proteins were consistently more abundant (by two-fold or greater) in ADPKD-uEVs than in healthy- and CKD-uEVs. Of these proteins, we selected periplakin, envoplakin, villin-1, and complement C3 and C9 for confirmation because they were also significantly overrepresented in pathway analysis and were previously implicated in ADPKD pathogenesis. Immunoblotting confirmed higher abundances of the selected proteins in uEVs from three independent groups of patients with ADPKD. Whereas uEVs of young patients with ADPKD and preserved kidney function already had higher levels of complement, only uEVs of patients with advanced stages of ADPKD had increased levels of villin-1, periplakin, and envoplakin. Furthermore, all five proteins correlated positively with total kidney volume. Analysis in kidney tissue from mice with kidney-specific, tamoxifen-inducible Pkd1 deletion demonstrated higher expression in more severe stages of the disease and correlation with kidney weight for each protein of interest. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.
[Mh] Termos MeSH primário: Complemento C3/fisiologia
Complemento C9/fisiologia
Vesículas Extracelulares
Plaquinas/fisiologia
Rim Policístico Autossômico Dominante/etiologia
Proteômica
Urina/química
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complement C3); 0 (Complement C9); 0 (Plakins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171001
[Lr] Data última revisão:
171001
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160305
[St] Status:MEDLINE


  8 / 765 MEDLINE  
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[PMID]:26902705
[Au] Autor:Guo B; Wu C; Lv Z; Liu C
[Ad] Endereço:National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316004, China. Electronic address: guobaoying@zjou.edu.cn.
[Ti] Título:Characterisation and expression analysis of two terminal complement components: C7 and C9 from large yellow croaker, Larimichthys crocea.
[So] Source:Fish Shellfish Immunol;51:211-219, 2016 Apr.
[Is] ISSN:1095-9947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The large yellow croaker Larimichthys crocea, as one of the most economically important marine fish in China and East Asian countries, are facing the fatal attraction of various pathogens in recent years. Elucidation of the organism immunomodulatory mechanism of croaker response to pathogen infection is essential for the disease control. In present study, we reported for the first time the molecular characterization and expression analysis of two terminal complement components (TCCs) of croaker, Lc-C7 and Lc-C9. These two structural conserved TCCs were detected in many tissues in adult healthy fish, with highest levels detected in liver. The transcriptional expression analysis of Lc-C7 and Lc-C9 at different developmental stages showed a continuous increase towards hatch, however the two TCCs mRNA were not detected at the unfertilized stage, hinting the origination of these two TCCs after fertilization. Rapid and drastic responses to Vibrio alginolyticus challenge were observed for Lc-C7 and Lc-C9, suggesting the involvement of component C7 and C9 in innate immune responses to pathogenic invasion in teleost fish. These findings could deepen our understanding about immunomodulatory mechanisms of croaker and shed a new light to the role of component system in teleostean immunomodulation.
[Mh] Termos MeSH primário: Complemento C7/imunologia
Complemento C9/imunologia
Doenças dos Peixes/imunologia
Proteínas de Peixes/imunologia
Perciformes/imunologia
Vibrioses/imunologia
Vibrio alginolyticus
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência de Bases
Complemento C7/genética
Complemento C9/genética
DNA Complementar/genética
Proteínas de Peixes/genética
Rim Cefálico/imunologia
Fígado/imunologia
Perciformes/genética
Filogenia
RNA Mensageiro/genética
Vibrioses/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Complement C7); 0 (Complement C9); 0 (DNA, Complementary); 0 (Fish Proteins); 0 (RNA, Messenger)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160224
[St] Status:MEDLINE


  9 / 765 MEDLINE  
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[PMID]:26841934
[Au] Autor:Dudkina NV; Spicer BA; Reboul CF; Conroy PJ; Lukoyanova N; Elmlund H; Law RH; Ekkel SM; Kondos SC; Goode RJ; Ramm G; Whisstock JC; Saibil HR; Dunstone MA
[Ad] Endereço:Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
[Ti] Título:Structure of the poly-C9 component of the complement membrane attack complex.
[So] Source:Nat Commun;7:10588, 2016 Feb 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major component of the MAC, a multi-protein complex that forms pores in the membrane of target pathogens. In contrast to homologous proteins such as perforin and the cholesterol-dependent cytolysins (CDCs), all of which require the membrane for oligomerisation, C9 assembles directly onto the nascent MAC from solution. However, the molecular mechanism of MAC assembly remains to be understood. Here we present the 8 Å cryo-EM structure of a soluble form of the poly-C9 component of the MAC. These data reveal a 22-fold symmetrical arrangement of C9 molecules that yield an 88-strand pore-forming ß-barrel. The N-terminal thrombospondin-1 (TSP1) domain forms an unexpectedly extensive part of the oligomerisation interface, thus likely facilitating solution-based assembly. These TSP1 interactions may also explain how additional C9 subunits can be recruited to the growing MAC subsequent to membrane insertion.
[Mh] Termos MeSH primário: Complemento C9/ultraestrutura
Complexo de Ataque à Membrana do Sistema Complemento/ultraestrutura
Polímeros
[Mh] Termos MeSH secundário: Microscopia Crioeletrônica
Seres Humanos
Modelos Moleculares
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Complement C9); 0 (Complement Membrane Attack Complex); 0 (Polymers)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160205
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms10588


  10 / 765 MEDLINE  
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[PMID]:26841837
[Au] Autor:Serna M; Giles JL; Morgan BP; Bubeck D
[Ad] Endereço:Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, South Kensington Campus, London SW7 2AZ, UK.
[Ti] Título:Structural basis of complement membrane attack complex formation.
[So] Source:Nat Commun;7:10587, 2016 Feb 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a 'multi-hit' mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a 'split-washer' configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular ß-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration.
[Mh] Termos MeSH primário: Complemento C5b/ultraestrutura
Complemento C6/ultraestrutura
Complemento C7/ultraestrutura
Complemento C8/ultraestrutura
Complemento C9/ultraestrutura
Complexo de Ataque à Membrana do Sistema Complemento/ultraestrutura
Complexos Multiproteicos/ultraestrutura
[Mh] Termos MeSH secundário: Cromatografia Líquida
Microscopia Crioeletrônica
Corantes Fluorescentes
Seres Humanos
Processamento de Imagem Assistida por Computador
Espectrometria de Massas
Microscopia Eletrônica
Modelos Moleculares
Estrutura Molecular
Estrutura Secundária de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Complement C6); 0 (Complement C7); 0 (Complement C8); 0 (Complement C9); 0 (Complement Membrane Attack Complex); 0 (Fluorescent Dyes); 0 (Multiprotein Complexes); 80295-55-2 (Complement C5b)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160205
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms10587



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