| Structural highlights
1gzy is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Related: | 1gzr, 1gzz, 1h02, 1h59, 1imx, 2gf1, 3gf1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[IGF1_HUMAN] Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
Function
[IGF1_HUMAN] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zoidis E, Ghirlanda-Keller C, Schmid C. Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I. Mol Cell Biochem. 2011 Feb;348(1-2):33-42. doi: 10.1007/s11010-010-0634-z. Epub, 2010 Nov 13. PMID:21076856 doi:10.1007/s11010-010-0634-z
- ↑ Brzozowski AM, Dodson EJ, Dodson GG, Murshudov GN, Verma C, Turkenburg JP, de Bree FM, Dauter Z. Structural origins of the functional divergence of human insulin-like growth factor-I and insulin. Biochemistry. 2002 Jul 30;41(30):9389-97. PMID:12135360
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