Open AccessG protein-coupled receptors: the evolution of structural insight
Author(s) -
Samantha B. Gacasan,
Daniel L. Baker,
Abby L. Parrill
Publication year - 2017
Publication title -
aims biophysics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.545
H-Index - 12
ISSN - 2377-9098
DOI - 10.3934/biophy.2017.3.491
Subject(s) - g protein coupled receptor , computational biology , allosteric regulation , superfamily , receptor , biology , drug discovery , structural biology , bioinformatics , biochemistry
G protein-coupled receptors (GPCR) comprise a diverse superfamily of over 800 proteins that have gained relevance as biological targets for pharmaceutical drug design. Although these receptors have been investigated for decades, three-dimensional structures of GPCR have only recently become available. In this review, we focus on the technological advancements that have facilitated efforts to gain insights into GPCR structure. Progress in these efforts began with the initial crystal structure determination of rhodopsin (PDB: 1F88) in 2000 and has continued to the most recently published structure of the A 1A R (PDB: 5UEN) in 2017. Numerous experimental developments over the past two decades have opened the door for widespread GPCR structural characterization. These efforts have resulted in the determination of three-dimensional structures for over 40 individual GPCR family members. Herein we present a comprehensive list and comparative analysis of over 180 individual GPCR structures. This includes a summary of different GPCR functional states crystallized with agonists, dual agonists, partial agonists, inverse agonists, antagonists, and allosteric modulators.