Structure Prediction of the Second Extracellular Loop in G-Protein-Coupled Receptors.

TitleStructure Prediction of the Second Extracellular Loop in G-Protein-Coupled Receptors.
Publication TypeJournal Article
Year of Publication2014
AuthorsKmiecik, Sebastian, Jamroz Michal, and Koliński Michał
JournalBiophys J
Volume106
Issue11
Pagination2408-2416
Date Published2014 Jun 3
ISSN1542-0086
Abstract<p>G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs.</p>
DOI10.1016/j.bpj.2014.04.022
Alternate JournalBiophys. J.
PubMed ID24896119