2hr7

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Template:STRUCTURE 2hr7

Insulin receptor (domains 1-3)

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The insulin receptor (IR) and the type-1 insulin-like growth factor receptor (IGF1R) are homologous multidomain proteins that bind insulin and IGF with differing specificity. Here we report the crystal structure of the first three domains (L1-CR-L2) of human IR at 2.3 A resolution and compare it with the previously determined structure of the corresponding fragment of IGF1R. The most important differences seen between the two receptors are in the two regions governing ligand specificity. The first is at the corner of the ligand-binding surface of the L1 domain, where the side chain of F39 in IR forms part of the ligand binding surface involving the second (central) beta-sheet. This is very different to the location of its counterpart in IGF1R, S35, which is not involved in ligand binding. The second major difference is in the sixth module of the CR domain, where IR contains a larger loop that protrudes further into the ligand-binding pocket. This module, which governs IGF1-binding specificity, shows negligible sequence identity, significantly more alpha-helix, an additional disulfide bond, and opposite electrostatic potential compared to that of the IGF1R.

Disease

Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]

About this Structure

2HR7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity., Lou M, Garrett TP, McKern NM, Hoyne PA, Epa VC, Bentley JD, Lovrecz GO, Cosgrove LJ, Frenkel MJ, Ward CW, Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12429-34. Epub 2006 Aug 7. PMID:16894147 Page seeded by OCA on Sun May 4 06:36:50 2008