Structural dynamics bridge the gap between the genetic and functional levels of GPCRs.

Mariona Torrens-Fontanals, Tomasz M Stepniewski, David E Gloriam, Jana Selent

Journal: Current opinion in structural biology 2021;69():150-159

PMID: 34052782

Full Text on Elsevier Science View on PubMed

Abstract

G protein-coupled receptors (GPCRs) are implicated in nearly all physiological processes in the human body and represent an important drug targeting class. The genes encoding the different GPCR (sub)types determine their specific functionality, which can be altered by natural genetic variants and isoforms. Deciphering the molecular link between sequence diversity and its functional consequences is a current challenge and critical for the comprehension of the physiological response of GPCRs. It requires a global understanding of how protein sequence translates into protein structure, how this impacts the structural motions of the protein, and, finally, how all these factors determine the receptor functionality. Here, we discuss available resources and state-of-the-art computational approaches to address this question.

Address: Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)-Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain.; Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)-Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain; InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland; Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, Poland.; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.; Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)-Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain. Electronic address: [email protected].

DOI: 10.1016/j.sbi.2021.04.005

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MeSH Terms: Amino Acid Sequence, Humans, Receptors, G-Protein-Coupled