7STH

Full-length insulin receptor bound with unsaturated insulin WT (2 insulin bound) symmetric conformation

7STH の概要

• エントリーDOI: 10.2210/pdb7sth/pdb
• EMDBエントリー: 25188 25189 25190 25191 25192 25193 25428
• 分子名称: Insulin receptor, Insulin (2 entities in total)
• 機能のキーワード: insulin receptor, site 1 binding deficient mutant insulin, signaling protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 335560.76

構造登録者

Bai, X.C.,Choi, E. (登録日: 2021-11-13, 公開日: 2022-03-30, 最終更新日: 2024-10-30)

主引用文献

Li, J.,Park, J.,Mayer, J.P.,Webb, K.J.,Uchikawa, E.,Wu, J.,Liu, S.,Zhang, X.,Stowell, M.H.B.,Choi, E.,Bai, X.C.
Synergistic activation of the insulin receptor via two distinct sites.
Nat.Struct.Mol.Biol., 29:357-368, 2022

PubMed Abstract: Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation.

PubMed: 35361965
DOI: 10.1038/s41594-022-00750-6

実験手法

ELECTRON MICROSCOPY (3.5 Å)