6fuf

Publication Abstract from PubMed

Selective coupling of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) to specific Galpha-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.

Crystal structure of rhodopsin in complex with a mini-Go sheds light on the principles of G protein selectivity.,Tsai CJ, Pamula F, Nehme R, Muhle J, Weinert T, Flock T, Nogly P, Edwards PC, Carpenter B, Gruhl T, Ma P, Deupi X, Standfuss J, Tate CG, Schertler GFX Sci Adv. 2018 Sep 19;4(9):eaat7052. doi: 10.1126/sciadv.aat7052. eCollection 2018, Sep. PMID:30255144^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.