{"title":"The role of Cysteine 6.47 in class A GPCRs","authors":"Mireia Olivella, Gianluigi Caltabiano, Arnau Cordomí","doi":"10.1186/1472-6807-13-3","DOIUrl":null,"url":null,"abstract":"<p>The CWxP motif of transmembrane helix 6 (x: any residue) is highly conserved in class A GPCRs. Within this motif, W6.48 is a big star in the theory of the global “toggle switch” because of its key role in the activation mechanism of GPCRs upon ligand binding. With all footlights focused on W6.48, the reason why the preceding residue, C6.47, is largely conserved is still unknown. The present study is aimed to fill up this lack of knowledge by characterizing the role of C6.47 of the CWxP motif.</p><p>A complete analysis of available crystal structures has been made alongside with molecular dynamics simulations of model peptides to explore a possible structural role for C6.47.</p><p>We conclude that C6.47 does not modulate the conformation of the TM6 proline kink and propose that C6.47 participates in the rearrangement of the TM6 and TM7 interface accompanying activation.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2013-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-3","citationCount":"32","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Structural Biology","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/1472-6807-13-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 32
Abstract
The CWxP motif of transmembrane helix 6 (x: any residue) is highly conserved in class A GPCRs. Within this motif, W6.48 is a big star in the theory of the global “toggle switch” because of its key role in the activation mechanism of GPCRs upon ligand binding. With all footlights focused on W6.48, the reason why the preceding residue, C6.47, is largely conserved is still unknown. The present study is aimed to fill up this lack of knowledge by characterizing the role of C6.47 of the CWxP motif.
A complete analysis of available crystal structures has been made alongside with molecular dynamics simulations of model peptides to explore a possible structural role for C6.47.
We conclude that C6.47 does not modulate the conformation of the TM6 proline kink and propose that C6.47 participates in the rearrangement of the TM6 and TM7 interface accompanying activation.
期刊介绍：
BMC Structural Biology is an open access, peer-reviewed journal that considers articles on investigations into the structure of biological macromolecules, including solving structures, structural and functional analyses, and computational modeling.
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