1IMX

1.8 Angstrom crystal structure of IGF-1

Summary for 1IMX

• Entry DOI: 10.2210/pdb1imx/pdb
• Descriptor: Insulin-like Growth Factor 1A, BROMIDE ION, N,N-BIS(3-D-GLUCONAMIDOPROPYL)DEOXYCHOLAMIDE, ... (4 entities in total)
• Functional Keywords: insulin/relaxin, detergent, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 8605.71

Authors

Vajdos, F.F.,Ultsch, M.,Schaffer, M.L.,Deshayes, K.D.,Liu, J.,Skelton, N.J.,de Vos, A.M. (deposition date: 2001-05-11, release date: 2001-09-05, Last modification date: 2024-11-20)

Primary citation

Vajdos, F.F.,Ultsch, M.,Schaffer, M.L.,Deshayes, K.D.,Liu, J.,Skelton, N.J.,de Vos, A.M.
Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions.
Biochemistry, 40:11022-11029, 2001

PubMed Abstract: 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.

PubMed: 11551198
DOI: 10.1021/bi0109111

Experimental method

X-RAY DIFFRACTION (1.82 Å)