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-Structure paper
Title | Structural insights into differences in G protein activation by family A and family B GPCRs. |
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Journal, issue, pages | Science, Vol. 369, Issue 6503, Year 2020 |
Publish date | Jul 31, 2020 |
Authors | Daniel Hilger / Kaavya Krishna Kumar / Hongli Hu / Mie Fabricius Pedersen / Evan S O'Brien / Lise Giehm / Christine Jennings / Gözde Eskici / Asuka Inoue / Michael Lerch / Jesper Mosolff Mathiesen / Georgios Skiniotis / Brian K Kobilka / |
PubMed Abstract | Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) play important roles in carbohydrate metabolism. Recent structures of family B GPCR-G protein ...Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) play important roles in carbohydrate metabolism. Recent structures of family B GPCR-G protein complexes reveal a disruption in the α-helix of transmembrane segment 6 (TM6) not observed in family A GPCRs. To investigate the functional impact of this structural difference, we compared the structure and function of the glucagon receptor (GCGR; family B) with the β adrenergic receptor (βAR; family A). We determined the structure of the GCGR-G complex by means of cryo-electron microscopy at 3.1-angstrom resolution. This structure shows the distinct break in TM6. Guanosine triphosphate (GTP) turnover, guanosine diphosphate release, GTP binding, and G protein dissociation studies revealed much slower rates for G protein activation by the GCGR compared with the βAR. Fluorescence and double electron-electron resonance studies suggest that this difference is due to the inability of agonist alone to induce a detectable outward movement of the cytoplasmic end of TM6. |
External links | Science / PubMed:32732395 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.1 Å |
Structure data | EMDB-21866, PDB-6wpw: |
Source |
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Keywords | SIGNALING PROTEIN/HORMONE/IMMUNE SYSTEM / GPCR / G protein / glucagon / signaling / complex / SIGNALING PROTEIN-HORMONE-IMMUNE SYSTEM complex |