2HR7

Insulin receptor (domains 1-3)

Summary for 2HR7

• Entry DOI: 10.2210/pdb2hr7/pdb
• Descriptor: Insulin receptor, 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL, GLYCEROL, ... (12 entities in total)
• Functional Keywords: hormone receptor, leucine rich repeat, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 122958.43

Authors

Garrett, T.P.J.,Ward, C.W. (deposition date: 2006-07-19, release date: 2006-08-15, Last modification date: 2024-10-09)

Primary citation

Lou, M.,Garrett, T.P.,McKern, N.M.,Hoyne, P.A.,Epa, V.C.,Bentley, J.D.,Lovrecz, G.O.,Cosgrove, L.J.,Frenkel, M.J.,Ward, C.W.
The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity.
Proc.Natl.Acad.Sci.Usa, 103:12429-12434, 2006

PubMed Abstract: 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.

PubMed: 16894147
DOI: 10.1073/pnas.0605395103

Experimental method

X-RAY DIFFRACTION (2.32 Å)