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PDBsum entry 1imx
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Hormone/growth factor
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PDB id
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1imx
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of human insulin-Like growth factor-1: detergent binding inhibits binding protein interactions.
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Authors
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F.F.Vajdos,
M.Ultsch,
M.L.Schaffer,
K.D.Deshayes,
J.Liu,
N.J.Skelton,
A.M.De vos.
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Ref.
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Biochemistry, 2001,
40,
11022-11029.
[DOI no: ]
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PubMed id
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Abstract
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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.
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