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Pesquisa : G05.360.340.024.340.425.420 [Categoria DeCS]
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[PMID]:28827448
[Au] Autor:Sundaram GM; Ismail HM; Bashir M; Muhuri M; Vaz C; Nama S; Ow GS; Vladimirovna IA; Ramalingam R; Burke B; Tanavde V; Kuznetsov V; Lane EB; Sampath P
[Ad] Endereço:Institute of Medical Biology, Agency for Science, Technology, and Research (A*STAR), Singapore.
[Ti] Título:EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis.
[So] Source:J Exp Med;214(10):2889-2900, 2017 Oct 02.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epithelial carcinomas are well known to activate a prolonged wound-healing program that promotes malignant transformation. Wound closure requires the activation of keratinocyte migration via a dual-state molecular switch. This switch involves production of either the anti-migratory microRNA miR-198 or the pro-migratory follistatin-like 1 (FSTL1) protein from a single transcript; miR-198 expression in healthy skin is down-regulated in favor of FSTL1 upon wounding, which enhances keratinocyte migration and promotes re-epithelialization. Here, we reveal a defective molecular switch in head and neck squamous cell carcinoma (HNSCC). This defect shuts off miR-198 expression in favor of sustained FSTL1 translation, driving metastasis through dual parallel pathways involving DIAPH1 and FSTL1. DIAPH1, a miR-198 target, enhances directional migration through sequestration of Arpin, a competitive inhibitor of Arp2/3 complex. FSTL1 blocks Wnt7a-mediated repression of extracellular signal-regulated kinase phosphorylation, enabling production of MMP9, which degrades the extracellular matrix and facilitates metastasis. The prognostic significance of the FSTL1-DIAPH1 gene pair makes it an attractive target for therapeutic intervention.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/metabolismo
Fator de Crescimento Epidérmico/fisiologia
Proteínas Relacionadas à Folistatina/fisiologia
MicroRNAs/fisiologia
Cicatrização/fisiologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Carcinoma de Células Escamosas/metabolismo
Proliferação Celular
Feminino
Genes de Troca/fisiologia
Neoplasias de Cabeça e Pescoço/metabolismo
Imunoprecipitação
Espectrometria de Massas
Camundongos Endogâmicos NOD
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Follistatin-Related Proteins); 0 (Fstl1 protein, mouse); 0 (MIRN198 microRNA, human); 0 (MIRN198 microRNA, mouse); 0 (MicroRNAs); 62229-50-9 (Epidermal Growth Factor)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20170354


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[PMID]:28525578
[Au] Autor:Hirosawa M; Fujita Y; Parr CJC; Hayashi K; Kashida S; Hotta A; Woltjen K; Saito H
[Ad] Endereço:Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
[Ti] Título:Cell-type-specific genome editing with a microRNA-responsive CRISPR-Cas9 switch.
[So] Source:Nucleic Acids Res;45(13):e118, 2017 Jul 27.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The CRISPR-Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR-Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells. Moreover, the miR-Cas9 switches could differentially control the genome editing by sensing endogenous miRNA activities within a heterogeneous cell population. Our miR-Cas9 switch system provides a promising framework for cell-type selective genome editing and cell engineering based on intracellular miRNA information.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas
Edição de Genes/métodos
MicroRNAs/genética
[Mh] Termos MeSH secundário: Regiões 5' não Traduzidas
Elementos Alu
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Diferenciação Celular
Técnicas de Cocultura
Endonucleases/genética
Endonucleases/metabolismo
Genes de Troca
Genes Sintéticos
Proteínas de Fluorescência Verde/genética
Células HeLa
Seres Humanos
Células-Tronco Pluripotentes Induzidas/citologia
Células-Tronco Pluripotentes Induzidas/metabolismo
MicroRNAs/metabolismo
Neurônios/citologia
Neurônios/metabolismo
RNA Guia/genética
RNA Guia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Bacterial Proteins); 0 (MicroRNAs); 0 (RNA, Guide); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 3.1.- (Cas9 endonuclease Streptococcus pyogenes); EC 3.1.- (Endonucleases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx309


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[PMID]:28512199
[Au] Autor:Villani R; Hodgson S; Legrand J; Greaney J; Wong HY; Pichol-Thievend C; Adolphe C; Wainwight B; Francois M; Khosrotehrani K
[Ad] Endereço:The University of Queensland, UQ Centre for Clinical Research, Royal Brisbane Hospital, Herston Road, Herston, Brisbane 4029, Queensland, Australia.
[Ti] Título:Dominant-negative function inhibits dermal papilla maturation and differentiation in all murine hair types.
[So] Source:Development;144(10):1887-1895, 2017 05 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types.
[Mh] Termos MeSH primário: Diferenciação Celular/genética
Folículo Piloso/embriologia
Cabelo/embriologia
Fatores de Transcrição SOXF/fisiologia
[Mh] Termos MeSH secundário: Animais
Derme/embriologia
Derme/metabolismo
Embrião de Mamíferos
Epiderme/citologia
Epiderme/embriologia
Feminino
Genes Dominantes
Genes de Troca/fisiologia
Cabelo/metabolismo
Folículo Piloso/metabolismo
Masculino
Camundongos
Camundongos Transgênicos
Fatores de Transcrição SOXF/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (SOXF Transcription Factors); 0 (Sox18 protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1242/dev.143917


  4 / 682 MEDLINE  
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[PMID]:27884016
[Au] Autor:De Smedt L; Palmans S; Andel D; Govaere O; Boeckx B; Smeets D; Galle E; Wouters J; Barras D; Suffiotti M; Dekervel J; Tousseyn T; De Hertogh G; Prenen H; Tejpar S; Lambrechts D; Sagaert X
[Ad] Endereço:Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
[Ti] Título:Expression profiling of budding cells in colorectal cancer reveals an EMT-like phenotype and molecular subtype switching.
[So] Source:Br J Cancer;116(1):58-65, 2017 Jan 03.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Tumour budding, described as the presence of single cells or small clusters of up to five tumour cells at the invasive margin, is established as a prognostic marker in colorectal carcinoma. In the present study, we aimed to investigate the molecular signature of tumour budding cells and the corresponding tumour bulk. METHODS: Tumour bulk and budding areas were microdissected and processed for RNA-sequencing. As little RNA was obtained from budding cells, a special low-input mRNA library preparation protocol was used. Gene expression profiles of budding as compared with tumour bulk were investigated for established EMT signatures, consensus molecular subtype (CMS), gene set enrichment and pathway analysis. RESULTS: A total of 296 genes were differentially expressed with an FDR <0.05 and a twofold change between tumour bulk and budding regions. Genes that were upregulated in the budding signature were mainly involved in cell migration and survival while downregulated genes were important for cell proliferation. Supervised clustering according to an established EMT gene signature categorised budding regions as EMT-positive, whereas tumour bulk was considered EMT-negative. Furthermore, a shift from CMS2 (epithelial) to CMS4 (mesenchymal) was observed as tumour cells transit from the tumour bulk to the budding regions. CONCLUSIONS: Tumour budding regions are characterised by a phenotype switch compared with the tumour bulk, involving the acquisition of migratory characteristics and a decrease in cell proliferation. In particular, most tumour budding signatures were EMT-positive and switched from an epithelial subtype (CMS2) in the tumour bulk to a mesenchymal subtype (CMS4) in budding cells.
[Mh] Termos MeSH primário: Divisão Celular/genética
Neoplasias Colorretais/genética
Neoplasias Colorretais/patologia
Transição Epitelial-Mesenquimal/genética
Genes de Troca/genética
Transcriptoma
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Proliferação Celular/genética
Neoplasias Colorretais/metabolismo
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Masculino
Margens de Excisão
Meia-Idade
Invasividade Neoplásica
Fenótipo
Análise Serial de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161125
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2016.382


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[PMID]:27768683
[Au] Autor:Perez-Carrasco R; Guerrero P; Briscoe J; Page KM
[Ad] Endereço:Department of Mathematics, University College London, Gower Street, London WC1E 6BT, UK.
[Ti] Título:Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches.
[So] Source:PLoS Comput Biol;12(10):e1005154, 2016 Oct.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively alter developmental patterning.
[Mh] Termos MeSH primário: Adaptação Fisiológica/genética
Regulação da Expressão Gênica no Desenvolvimento/genética
Genes de Troca/genética
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Modelos Genéticos
Morfogênese/genética
[Mh] Termos MeSH secundário: Animais
Simulação por Computador
Homeostase/genética
Seres Humanos
Modelos Estatísticos
Razão Sinal-Ruído
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intercellular Signaling Peptides and Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161022
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005154


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[PMID]:27711197
[Au] Autor:Anderson MZ; Porman AM; Wang N; Mancera E; Huang D; Cuomo CA; Bennett RJ
[Ad] Endereço:Department of Microbiology and Immunology, Brown University, Providence, Rhode Island, United States of America.
[Ti] Título:A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues.
[So] Source:PLoS Genet;12(10):e1006353, 2016 Oct.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming.
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/genética
Epigênese Genética
Proteínas Fúngicas/biossíntese
Genes de Troca/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Candida albicans/genética
Candida albicans/crescimento & desenvolvimento
Candida tropicalis/genética
Candida tropicalis/crescimento & desenvolvimento
Diferenciação Celular/genética
Linhagem da Célula/genética
Cromatina/genética
Proteínas de Ligação a DNA/biossíntese
Proteínas Fúngicas/genética
Regulação da Expressão Gênica no Desenvolvimento
Regulação Fúngica da Expressão Gênica
Fatores de Transcrição/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (DNA-Binding Proteins); 0 (EFG1 protein, Candida albicans); 0 (Fungal Proteins); 0 (Transcription Factors)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161007
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006353


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[PMID]:27436344
[Au] Autor:Ragsdale EJ; Ivers NA
[Ad] Endereço:Department of Biology, Indiana University, Bloomington, Indiana, 47405. ragsdale@indiana.edu.
[Ti] Título:Specialization of a polyphenism switch gene following serial duplications in Pristionchus nematodes.
[So] Source:Evolution;70(9):2155-66, 2016 Sep.
[Is] ISSN:1558-5646
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Polyphenism is an extreme manifestation of developmental plasticity, requiring distinct developmental programs and the addition of a switch mechanism. Because the genetic basis of polyphenism switches has only begun to be understood, how their mechanisms arise is unclear. In the nematode Pristionchus pacificus, which has a mouthpart polyphenism specialized for alternative diets, a gene (eud-1) executing the polyphenism switch was recently identified as the product of lineage-specific duplications. Here, we infer the role of gene duplications in producing a switch gene. Using reverse genetics and population genetic analyses, we examine evidence for competing scenarios of degeneration and complementation, neutral evolution, and functional specialization. Of the daughter genes, eud-1 alone has assumed switch-like regulation of the mouth polyphenism. Measurements of life-history traits in single, double, and triple sulfatase mutants did not, given a benign environment, identify alternative or complementary roles for eud-1 paralogs. Although possible roles are still unknown, selection analyses of the sister species and 104 natural isolates of P. pacificus detected purifying selection on the genes, suggesting their functionality by their fixation and evolutionary maintenance. Our approach shows the tractability of reverse genetics in a nontraditional model system to study evolution by gene duplication.
[Mh] Termos MeSH primário: Duplicação Gênica
Genes de Troca
Fenótipo
Rabditídios/genética
[Mh] Termos MeSH secundário: Animais
Evolução Biológica
Proteínas de Helminto/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Helminth Proteins)
[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:160721
[St] Status:MEDLINE
[do] DOI:10.1111/evo.13011


  8 / 682 MEDLINE  
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[PMID]:27280690
[Au] Autor:Lohse MB; Ene IV; Craik VB; Hernday AD; Mancera E; Morschhäuser J; Bennett RJ; Johnson AD
[Ad] Endereço:Department of Microbiology and Immunology, University of California, San Francisco, California 94158.
[Ti] Título:Systematic Genetic Screen for Transcriptional Regulators of the Candida albicans White-Opaque Switch.
[So] Source:Genetics;203(4):1679-92, 2016 Aug.
[Is] ISSN:1943-2631
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human fungal pathogen Candida albicans can reversibly switch between two cell types named "white" and "opaque," each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A highly interconnected network of eight transcriptional regulators has been shown to control switching between these two cell types. To identify additional regulators of the switch, we systematically and quantitatively measured white-opaque switching rates of 196 strains, each deleted for a specific transcriptional regulator. We identified 19 new regulators with at least a 10-fold effect on switching rates and an additional 14 new regulators with more subtle effects. To investigate how these regulators affect switching rates, we examined several criteria, including the binding of the eight known regulators of switching to the control region of each new regulatory gene, differential expression of the newly found genes between cell types, and the growth rate of each mutant strain. This study highlights the complexity of the transcriptional network that regulates the white-opaque switch and the extent to which switching is linked to a variety of metabolic processes, including respiration and carbon utilization. In addition to revealing specific insights, the information reported here provides a foundation to understand the highly complex coupling of white-opaque switching to cellular physiology.
[Mh] Termos MeSH primário: Candida albicans/genética
Genes Fúngicos Tipo Acasalamento/genética
Elementos Reguladores de Transcrição/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Candida albicans/crescimento & desenvolvimento
Candida albicans/patogenicidade
Epigênese Genética
Regulação Fúngica da Expressão Gênica
Redes Reguladoras de Genes/genética
Genes de Troca
Seres Humanos
Fatores de Transcrição/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Transcription Factors)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160610
[St] Status:MEDLINE
[do] DOI:10.1534/genetics.116.190645


  9 / 682 MEDLINE  
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[PMID]:27253392
[Au] Autor:Sikosek T; Krobath H; Chan HS
[Ad] Endereço:Departments of Biochemistry and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches.
[So] Source:PLoS Comput Biol;12(6):e1004960, 2016 06.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Deciphering the effects of nonsynonymous mutations on protein structure is central to many areas of biomedical research and is of fundamental importance to the study of molecular evolution. Much of the investigation of protein evolution has focused on mutations that leave a protein's folded structure essentially unchanged. However, to evolve novel folds of proteins, mutations that lead to large conformational modifications have to be involved. Unraveling the basic biophysics of such mutations is a challenge to theory, especially when only one or two amino acid substitutions cause a large-scale conformational switch. Among the few such mutational switches identified experimentally, the one between the GA all-α and GB α+ß folds is extensively characterized; but all-atom simulations using fully transferrable potentials have not been able to account for this striking switching behavior. Here we introduce an explicit-chain model that combines structure-based native biases for multiple alternative structures with a general physical atomic force field, and apply this construct to twelve mutants spanning the sequence variation between GA and GB. In agreement with experiment, we observe conformational switching from GA to GB upon a single L45Y substitution in the GA98 mutant. In line with the latent evolutionary potential concept, our model shows a gradual sequence-dependent change in fold preference in the mutants before this switch. Our analysis also indicates that a sharp GA/GB switch may arise from the orientation dependence of aromatic π-interactions. These findings provide physical insights toward rationalizing, predicting and designing evolutionary conformational switches.
[Mh] Termos MeSH primário: Evolução Molecular
Proteínas de Ligação ao GTP/química
Proteínas de Ligação ao GTP/genética
Genes de Troca/genética
Instabilidade Genômica/genética
Modelos Químicos
[Mh] Termos MeSH secundário: Simulação por Computador
Proteínas de Ligação ao GTP/ultraestrutura
Variação Genética
Modelos Genéticos
Modelos Moleculares
Conformação Proteica
Dobramento de Proteína
Análise de Sequência de Proteína/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170320
[Lr] Data última revisão:
170320
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160603
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1004960


  10 / 682 MEDLINE  
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[PMID]:27155656
[Au] Autor:Chen H; Thill P; Cao J
[Ad] Endereço:Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
[Ti] Título:Transitions in genetic toggle switches driven by dynamic disorder in rate coefficients.
[So] Source:J Chem Phys;144(17):175104, 2016 May 07.
[Is] ISSN:1089-7690
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In biochemical systems, intrinsic noise may drive the system switch from one stable state to another. We investigate how kinetic switching between stable states in a bistable network is influenced by dynamic disorder, i.e., fluctuations in the rate coefficients. Using the geometric minimum action method, we first investigate the optimal transition paths and the corresponding minimum actions based on a genetic toggle switch model in which reaction coefficients draw from a discrete probability distribution. For the continuous probability distribution of the rate coefficient, we then consider two models of dynamic disorder in which reaction coefficients undergo different stochastic processes with the same stationary distribution. In one, the kinetic parameters follow a discrete Markov process and in the other they follow continuous Langevin dynamics. We find that regulation of the parameters modulating the dynamic disorder, as has been demonstrated to occur through allosteric control in bistable networks in the immune system, can be crucial in shaping the statistics of optimal transition paths, transition probabilities, and the stationary probability distribution of the network.
[Mh] Termos MeSH primário: Genes de Troca
Modelos Biológicos
Processos Estocásticos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170507
[Lr] Data última revisão:
170507
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160509
[St] Status:MEDLINE
[do] DOI:10.1063/1.4948461



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