7AD3

Class D GPCR Ste2 dimer coupled to two G proteins

Summary for 7AD3

• Entry DOI: 10.2210/pdb7ad3/pdb
• EMDB information: 11720
• Descriptor: Pheromone alpha factor receptor, Alpha-factor mating pheromone, STE4 isoform 1, ... (7 entities in total)
• Functional Keywords: fungal gpcr, dimer, complex, class d, active state, membrane protein
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 8
• Total formula weight: 214242.16

Authors

Velazhahan, V.,Tate, C. (deposition date: 2020-09-14, release date: 2020-12-09, Last modification date: 2024-11-13)

Primary citation

Velazhahan, V.,Ma, N.,Pandy-Szekeres, G.,Kooistra, A.J.,Lee, Y.,Gloriam, D.E.,Vaidehi, N.,Tate, C.G.
Structure of the class D GPCR Ste2 dimer coupled to two G proteins.
Nature, 589:148-153, 2021

PubMed Abstract: G-protein-coupled receptors (GPCRs) are divided phylogenetically into six classes, 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. 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 diseases.

PubMed: 33268889
DOI: 10.1038/s41586-020-2994-1

Experimental method

ELECTRON MICROSCOPY (3.5 Å)