6PXV

Cryo-EM structure of full-length insulin receptor bound to 4 insulin. 3D refinement was focused on the extracellular region.

6PXV の概要

• エントリーDOI: 10.2210/pdb6pxv/pdb
• EMDBエントリー: 20522 20523
• 分子名称: Insulin receptor, Insulin (2 entities in total)
• 機能のキーワード: insulin receptor, insulin, signaling protein-hormone complex, signaling protein/hormone
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 341348.74

構造登録者

Uchikawa, E.,Choi, E.,Shang, G.J.,Yu, H.T.,Bai, X.C. (登録日: 2019-07-27, 公開日: 2019-09-04, 最終更新日: 2024-10-23)

主引用文献

Uchikawa, E.,Choi, E.,Shang, G.,Yu, H.,Bai, X.C.
Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex.
Elife, 8:-, 2019

PubMed Abstract: Insulin signaling controls metabolic homeostasis. Here, we report the cryo-EM structure of full-length insulin receptor (IR) and insulin complex in the active state. This structure unexpectedly reveals that maximally four insulins can bind the 'T'-shaped IR dimer at four distinct sites related by 2-fold symmetry. Insulins 1 and 1' bind to sites 1 and 1', formed by L1 of one IR protomer and α-CT and FnIII-1 of the other. Insulins 2 and 2' bind to sites 2 and 2' on FnIII-1 of each protomer. Mutagenesis and cellular assays show that both sites 1 and 2 are required for optimal insulin binding and IR activation. We further identify a homotypic FnIII-2-FnIII-2 interaction in mediating the dimerization of membrane proximal domains in the active IR dimer. Our results indicate that binding of multiple insulins at two distinct types of sites disrupts the autoinhibited apo-IR dimer and stabilizes the active dimer.

PubMed: 31436533
DOI: 10.7554/eLife.48630

実験手法

ELECTRON MICROSCOPY (3.2 Å)