6B20

Crystal structure of a complex between G protein beta gamma dimer and an inhibitory Nanobody regulator

6B20 の概要

• エントリーDOI: 10.2210/pdb6b20/pdb
• 分子名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(T) subunit gamma-T1, Nanobody against G protein beta gamma dimer, ... (6 entities in total)
• 機能のキーワード: beta propeller, g protein, g protein coupled receptor-signaling, signaling protein
• 由来する生物種: Bos taurus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 113232.44

構造登録者

Gulati, S.,Kiser, P.D.,Palczewski, K. (登録日: 2017-09-19, 公開日: 2018-05-30, 最終更新日: 2024-10-16)

主引用文献

Gulati, S.,Jin, H.,Masuho, I.,Orban, T.,Cai, Y.,Pardon, E.,Martemyanov, K.A.,Kiser, P.D.,Stewart, P.L.,Ford, C.P.,Steyaert, J.,Palczewski, K.
Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor.
Nat Commun, 9:1996-1996, 2018

PubMed Abstract: G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Gα subunit. This leads to dissociation of the heterotrimer into Gα-GTP and Gβγ dimer. The Gα-GTP and Gβγ dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gβγ-signaling is a central element of various neurological and cancer-related anomalies. However, Gβγ also serves as a negative regulator of Gα that is essential for G protein inactivation, and thus has the potential for numerous side effects when targeted therapeutically. Here we report a llama-derived nanobody (Nb5) that binds tightly to the Gβγ dimer. Nb5 responds to all combinations of β-subtypes and γ-subtypes and competes with other Gβγ-regulatory proteins for a common binding site on the Gβγ dimer. Despite its inhibitory effect on Gβγ-mediated signaling, Nb5 has no effect on Gα-mediated and Gα-mediated signaling events in living cells.

PubMed: 29777099
DOI: 10.1038/s41467-018-04432-0

実験手法

X-RAY DIFFRACTION (2.34 Å)