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
Released Data Link
Team
Principal Investigator
Co-Investigator(s)