Structure of the class D GPCR Ste2 dimer coupled to two G proteins
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ABSTRACT:
SUBMITTER: Vaithish Velazhahan
PROVIDER: EMPIAR-10550 | biostudies-other |
REPOSITORIES: biostudies-other
Publications
Structure of the class D GPCR Ste2 dimer coupled to two G proteins.
Velazhahan Vaithish V Ma Ning N Pándy-Szekeres Gáspár G Kooistra Albert J AJ Lee Yang Y Gloriam David E DE Vaidehi Nagarajan N Tate Christopher G CG
Nature 20201202 7840
G-protein-coupled receptors (GPCRs) are divided phylogenetically into six classes<sup>1,2</sup>, denoted A to F. More than 370 structures of vertebrate GPCRs (belonging to classes A, B, C and F) have been determined, leading to a substantial understanding of their function<sup>3</sup>. By contrast, there are no structures of class D GPCRs, which are found exclusively in fungi where they regulate survival and reproduction. Here we determine the structure of a class D GPCR, the Saccharomyces cerev ...[more]
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Project description:G-protein-coupled receptors (GPCRs) are divided phylogenetically into six classes1,2, denoted A to F. More than 370 structures of vertebrate GPCRs (belonging to classes A, B, C and F) have been determined, leading to a substantial understanding of their function3. By contrast, there are no structures of class D GPCRs, which are found exclusively in fungi where they regulate survival and reproduction. Here we determine the structure of a class D GPCR, the Saccharomyces cerevisiae pheromone receptor Ste2, in an active state coupled to the heterotrimeric G protein Gpa1-Ste4-Ste18. Ste2 was purified as a homodimer coupled to two G proteins. The dimer interface of Ste2 is formed by the N terminus, the transmembrane helices H1, H2 and H7, and the first extracellular loop ECL1. We establish a class D1 generic residue numbering system (CD1) to enable comparisons with orthologues and with other GPCR classes. The structure of Ste2 bears similarities in overall topology to class A GPCRs, but the transmembrane helix H4 is shifted by more than 20 Å and the G-protein-binding site is a shallow groove rather than a cleft. The structure provides a template for the design of novel drugs to target fungal GPCRs, which could be used to treat numerous intractable fungal diseases4.
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