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1gzz
From Proteopedia
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HUMAN INSULIN-LIKE GROWTH FACTOR; HAMBURG DATA
Contents |
Overview
Human insulin-like growth factors I and II (hIGF-I, hIGF-II) are potent stimulators of cell and growth processes. They display high sequence similarity to both the A and B chains of insulin but contain an additional connecting C-domain, which reflects their secretion without specific packaging or precursor conversion. IGFs also have an extension at the C-terminus known as the D-domain. This paper describes four homologous hIGF-1 structures, obtained from crystals grown in the presence of the detergent SB12, which reveal additional detail in the C- and D-domains. Two different detergent binding modes observed in the crystals may reflect different hIGF-I biological properties such as the interaction with IGF binding proteins and self-aggregation. While the helical core of hIGF-I is very similar to that in insulin, there are distinct differences in the region of hIGF-I corresponding to the insulin B chain C-terminus, residues B25-B30. In hIGF-I, these residues (24-29) and the following C-domain form an extensive loop protruding 20 A from the core, which results in a substantially different conformation for the receptor binding epitope in hIGF-I compared to insulin. One notable feature of the structures presented here is demonstration of peptide-bond cleavage between Ser35 and Arg36 resulting in an apparent gap between residues 35 and 39. The equivalent region of proinsulin is involved in hormone processing demanding a reassessment of the structural integrity of hIGF-I in relation to its biological function.
Disease
Known disease associated with this structure: Growth retardation with deafness and mental retardation due to IGF1 deficiency OMIM:[147440]
About this Structure
1GZZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural origins of the functional divergence of human insulin-like growth factor-I and insulin., Brzozowski AM, Dodson EJ, Dodson GG, Murshudov GN, Verma C, Turkenburg JP, de Bree FM, Dauter Z, Biochemistry. 2002 Jul 30;41(30):9389-97. PMID:12135360
Page seeded by OCA on Thu Mar 20 11:30:19 2008
