Crystal structure of rhodopsin in complex with a mini-Go sheds light on the principles of G protein selectivity

Open access
Date
2018-09-05Type
- Journal Article
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Cited 37 times in
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Cited 39 times in
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Abstract
Selective coupling of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) to specific Gα-protein subtypes is critical to transform extracellular signals, carried by natural ligands and clinical drugs, into cellular responses. At the center of this transduction event lies the formation of a signaling complex between the receptor and G protein. We report the crystal structure of light-sensitive GPCR rhodopsin bound to an engineered mini-Go protein. The conformation of the receptor is identical to all previous structures of active rhodopsin, including the complex with arrestin. Thus, rhodopsin seems to adopt predominantly one thermodynamically stable active conformation, effectively acting like a “structural switch,” allowing for maximum efficiency in the visual system. Furthermore, our analysis of the well-defined GPCR–G protein interface suggests that the precise position of the carboxyl-terminal “hook-like” element of the G protein (its four last residues) relative to the TM7/helix 8 (H8) joint of the receptor is a significant determinant in selective G protein activation. Show more
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https://doi.org/10.3929/ethz-b-000295633Publication status
publishedExternal links
Journal / series
Science AdvancesVolume
Pages / Article No.
Publisher
AAASFunding
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Is part of: https://doi.org/10.3929/ethz-b-000428587
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Citations
Cited 37 times in
Web of Science
Cited 39 times in
Scopus
ETH Bibliography
yes
Altmetrics