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Insulin receptor-peptide agonist structures


EMSL Project ID
50677

Abstract

Our goal is to determine the structure of the insulin receptor (IR) ectodomain bound to non-insulin peptide modulators of the receptor. We are studying two peptides which share a high degree of sequence similarity with each other. We believe that both peptides are interacting the two known binding sites of the insulin receptor. However, only one of the two peptides are able to induce the conformational change that is known to be associated with the active state of the receptor. Therefore, one peptide is an agonist of the insulin receptor while the other one is an antagonist. Furthermore, we believe the peptide agonist induces a biased signaling transduction compared to native human insulin. Ultimately, a detailed molecular model of how these non-insulin peptides engage the insulin receptor will expand the templates for structure-based design of drugs targeting insulin receptor, as well as reveal a mechanism for biased agonism at the insulin receptor.

Project Details

Start Date
2019-01-14
End Date
2019-04-30
Status
Closed

Team

Principal Investigator

Christopher Hill
Institution
University of Utah

Co-Investigator(s)

Heidi Schubert
Institution
University of Utah