The role of G protein conformation in receptor–G protein selectivity

被引:0
作者
Wonjo Jang
Sumin Lu
Xin Xu
Guangyu Wu
Nevin A. Lambert
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[1] Augusta University,Department of Pharmacology and Toxicology, Medical College of Georgia
来源
Nature Chemical Biology | 2023年 / 19卷
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摘要
G protein-coupled receptors (GPCRs) selectively activate at least one of the four families of heterotrimeric G proteins, but the mechanism of coupling selectivity remains unclear. Structural studies emphasize structural complementarity of GPCRs and nucleotide-free G proteins, but selectivity is likely to be determined by transient intermediate-state complexes that exist before nucleotide release. Here we study coupling to nucleotide-decoupled G protein variants that can adopt conformations similar to receptor-bound G proteins without releasing nucleotide, and are therefore able to bypass intermediate-state complexes. We find that selectivity is degraded when nucleotide release is not required for GPCR–G protein complex formation, to the extent that most GPCRs interact with most nucleotide-decoupled G proteins. These findings demonstrate the absence of absolute structural incompatibility between noncognate receptor–G protein pairs, and are consistent with the hypothesis that transient intermediate states are partly responsible for coupling selectivity.
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页码:687 / 694
页数:7
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