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IR-A agonist structures


EMSL Project ID
51374

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 that share a high degree of sequence similarity but result in either agonistic or antagonistic effects. Importantly, the agonistic peptide preferentially induces the metabolic effects of IR activation over the mitogenic effects of IR signaling, through a mechanism that appears to involve an as-of-yet undescribed receptor conformation. 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
2020-05-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Christopher Hill
Institution
University of Utah

Team Members

Nancy Meyer
Institution
Oregon Health & Science University

Heidi Schubert
Institution
University of Utah