6SOF

human insulin receptor ectodomain bound by 4 insulin

6SOF の概要

• エントリーDOI: 10.2210/pdb6sof/pdb
• EMDBエントリー: 10273
• 分子名称: Insulin receptor, Insulin, ... (4 entities in total)
• 機能のキーワード: cell surface receptor, insulin, tyrosine kinase receptor, glucose homeostasis, hormone, diabetes, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 225401.89

構造登録者

Gutmann, T.,Schaefer, I.B.,Poojari, C.S.,Vattulainen, I.,Strauss, M.,Coskun, U. (登録日: 2019-08-29, 公開日: 2019-11-13, 最終更新日: 2024-10-23)

主引用文献

Gutmann, T.,Schafer, I.B.,Poojari, C.,Brankatschk, B.,Vattulainen, I.,Strauss, M.,Coskun, U.
Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain.
J.Cell Biol., 219:-, 2020

PubMed Abstract: Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand-receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have resolved only site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we present the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin-site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis for a comprehensive description of ligand-receptor interactions that ultimately will inform new approaches to structure-based drug design.

PubMed: 31727777
DOI: 10.1083/jcb.201907210

実験手法

ELECTRON MICROSCOPY (4.3 Å)