6MHF

Galphai3 co-crystallized with GIV/Girdin

6MHF の概要

• エントリーDOI: 10.2210/pdb6mhf/pdb
• 分子名称: Guanine nucleotide-binding protein G(k) subunit alpha, Girdin, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: exchange, modulator, gpcr, inhibitory, signaling protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43914.37

構造登録者

Rees, S.D.,Kalogriopoulos, N.A.,Ngo, T.,Kopcho, N.,Ilatovskiy, A.,Sun, N.,Komives, E.,Chang, G.,Ghosh, P.,Kufareva, I. (登録日: 2018-09-17, 公開日: 2019-07-31, 最終更新日: 2023-10-11)

主引用文献

Kalogriopoulos, N.A.,Rees, S.D.,Ngo, T.,Kopcho, N.J.,Ilatovskiy, A.V.,Sun, N.,Komives, E.A.,Chang, G.,Ghosh, P.,Kufareva, I.
Structural basis for GPCR-independent activation of heterotrimeric Gi proteins.
Proc.Natl.Acad.Sci.USA, 116:16394-16403, 2019

PubMed Abstract: Heterotrimeric G proteins are key molecular switches that control cell behavior. The canonical activation of G proteins by agonist-occupied G protein-coupled receptors (GPCRs) has recently been elucidated from the structural perspective. In contrast, the structural basis for GPCR-independent G protein activation by a novel family of guanine-nucleotide exchange modulators (GEMs) remains unknown. Here, we present a 2.0-Å crystal structure of Gαi in complex with the GEM motif of GIV/Girdin. Nucleotide exchange assays, molecular dynamics simulations, and hydrogen-deuterium exchange experiments demonstrate that GEM binding to the conformational switch II causes structural changes that allosterically propagate to the hydrophobic core of the Gαi GTPase domain. Rearrangement of the hydrophobic core appears to be a common mechanism by which GPCRs and GEMs activate G proteins, although with different efficiency. Atomic-level insights presented here will aid structure-based efforts to selectively target the noncanonical G protein activation.

PubMed: 31363053
DOI: 10.1073/pnas.1906658116

実験手法

X-RAY DIFFRACTION (2 Å)