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-Structure paper
タイトル | Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain. |
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ジャーナル・号・ページ | J Cell Biol, Vol. 219, Issue 1, Year 2020 |
掲載日 | 2020年1月6日 |
![]() | Theresia Gutmann / Ingmar B Schäfer / Chetan Poojari / Beate Brankatschk / Ilpo Vattulainen / Mike Strauss / Ünal Coskun / ![]() ![]() ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 4.3 - 5.0 Å |
構造データ | EMDB-10273, PDB-6sof: EMDB-10311: Human insulin receptor ectodomain bound by several insulins in an intermediate state |
由来 |
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![]() | MEMBRANE PROTEIN / cell surface receptor / insulin / tyrosine kinase receptor / glucose homeostasis / hormone / diabetes |