Crystal Structure of Human Insulin-like Growth Factor-1: Detergent Binding Inhibits Binding Protein Interactions
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- 作者：Felix F. Vajdos ; Mark Ultsch ; Michelle L. Schaffer ; Kurt D. Deshayes ; Jun Liu ; Nicholas J. Skelton ; and Abraham M. de Vos
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：September 18, 2001
- 年：2001
- 卷：40
- 期：37
- 页码：11022 - 11029
- 全文大小：336K
- 年卷期：v.40,no.37(September 18, 2001)
- ISSN：1520-4995
文摘
Despite efforts spanning considerably more than a decade, a high-resolution view of the familyof proteins known as insulin-like growth factors (IGFs) has remained elusive. IGF-1 consists of threehelical segments which are connected by a 12-residue linker known as the C-region. NMR studies ofmembers of this family reveal a dynamic structure with a topology resembling insulin but little structuraldefinition 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 Å resolution by multiwavelength anomalous diffraction, exploiting theanomalous scattering of a single bromide ion and six of the seven sulfur atoms of IGF-1. The structurereveals a well-defined conformation for much of the C-region, which extends away from the core ofIGF-1 and has residues known to be involved in receptor binding prominently displayed in a type II
-turn. In the crystal, these residues form a dimer interface, but analytical ultracentrifugation experimentsdemonstrate that at physiological concentrations IGF-1 is monomeric. A single detergent molecule contactsresidues known to be important for IGF-1 binding protein (IGFBP) interactions. Biophysical andbiochemical data show that the detergent binds to IGF-1 specifically and blocks binding of IGFBP-1 andIGFBP-3.
-turn. In the crystal, these residues form a dimer interface, but analytical ultracentrifugation experimentsdemonstrate that at physiological concentrations IGF-1 is monomeric. A single detergent molecule contactsresidues known to be important for IGF-1 binding protein (IGFBP) interactions. Biophysical andbiochemical data show that the detergent binds to IGF-1 specifically and blocks binding of IGFBP-1 andIGFBP-3.