6SOF

human insulin receptor ectodomain bound by 4 insulin

Summary for 6SOF

• Entry DOI: 10.2210/pdb6sof/pdb
• EMDB information: 10273
• Descriptor: Insulin receptor, Insulin, ... (4 entities in total)
• Functional Keywords: cell surface receptor, insulin, tyrosine kinase receptor, glucose homeostasis, hormone, diabetes, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 225401.89

Authors

Gutmann, T.,Schaefer, I.B.,Poojari, C.S.,Vattulainen, I.,Strauss, M.,Coskun, U. (deposition date: 2019-08-29, release date: 2019-11-13, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (4.3 Å)