1imx

Categories: Homo sapiens | Single protein | Deshayes, K D. | Liu, J. | Schaffer, M L. | Skelton, N J. | Ultsch, M. | Vajdos, F F. | Vos, A M.de. | BR | CPQ | Detergent | Insulin/relaxin

1.8 Angstrom crystal structure of IGF-1

Overview

Despite efforts spanning considerably more than a decade, a high-resolution view of the family of proteins known as insulin-like growth factors (IGFs) has remained elusive. IGF-1 consists of three helical segments which are connected by a 12-residue linker known as the C-region. NMR studies of members of this family reveal a dynamic structure with a topology resembling insulin but little structural definition in the C-region. We have crystallized IGF-1 in the presence of the detergent deoxy big CHAPS, and determined its structure at 1.8 A resolution by multiwavelength anomalous diffraction, exploiting the anomalous scattering of a single bromide ion and six of the seven sulfur atoms of IGF-1. The structure reveals a well-defined conformation for much of the C-region, which extends away from the core of IGF-1 and has residues known to be involved in receptor binding prominently displayed in a type II beta-turn. In the crystal, these residues form a dimer interface, but analytical ultracentrifugation experiments demonstrate that at physiological concentrations IGF-1 is monomeric. A single detergent molecule contacts residues known to be important for IGF-1 binding protein (IGFBP) interactions. Biophysical and biochemical data show that the detergent binds to IGF-1 specifically and blocks binding of IGFBP-1 and IGFBP-3.

Disease

Known disease associated with this structure: Growth retardation with deafness and mental retardation due to IGF1 deficiency OMIM:[147440]

About this Structure

1IMX is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions., Vajdos FF, Ultsch M, Schaffer ML, Deshayes KD, Liu J, Skelton NJ, de Vos AM, Biochemistry. 2001 Sep 18;40(37):11022-9. PMID:11551198

Page seeded by OCA on Thu Feb 21 13:13:34 2008