Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models

[thumbnail of 17445oa.PDF]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
900kB

Item Type:Article
Title:Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models
Creators Name:Worth, C.L., Kleinau, G. and Krause, G.
Abstract:BACKGROUND: Up until recently the only available experimental (high resolution) structure of a G-protein-coupled receptor (GPCR) was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s) to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. METHODOLOGY: We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s) for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s) for building a comparative molecular model. CONCLUSIONS: The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying suitable templates for GPCR homology modelling that will help to produce more reliable three-dimensional models.
Keywords:Amino Acid Motifs, Amino Acid Sequence, DNA Mutational Analysis, Decapodiformes, Disulfides, Molecular Conformation, Molecular Sequence Data, Phylogeny, Protein Conformation, Secondary Protein Structure, G-Protein-Coupled Receptors, Rhodopsin, Amino Acid Sequence Homology, X-Ray Crystallography, Animals
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:4
Number:9
Page Range:e7011
Date:16 September 2009
Official Publication:https://doi.org/10.1371/journal.pone.0007011
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library