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-Structure paper
Title | Structure of the class D GPCR Ste2 dimer coupled to two G proteins. |
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Journal, issue, pages | Nature, Vol. 589, Issue 7840, Page 148-153, Year 2021 |
Publish date | Dec 2, 2020 |
Authors | Vaithish Velazhahan / Ning Ma / Gáspár Pándy-Szekeres / Albert J Kooistra / Yang Lee / David E Gloriam / Nagarajan Vaidehi / Christopher G Tate / |
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 ...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. |
External links | Nature / PubMed:33268889 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.7 - 3.53 Å |
Structure data | EMDB-11720, PDB-7ad3: EMDB-13880, PDB-7qa8: EMDB-13882, PDB-7qb9: EMDB-13886, PDB-7qbc: EMDB-13887, PDB-7qbi: |
Chemicals | ChemComp-NAG: ChemComp-Y01: ChemComp-HOH: |
Source |
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Keywords | MEMBRANE PROTEIN / Fungal GPCR / Dimer / Complex / Class D / Active State / GPCR / antagonist-bound / fungal / ligand-free / agonist-bound |