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| [[Image:1h02.gif|left|200px]] | | [[Image:1h02.png|left|200px]] |
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| ==Overview==
| | {{ABSTRACT_12135360}} |
| 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.
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| ==About this Structure== | | ==About this Structure== |
| 1H02 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1H02 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb52_1.html Growth Hormone]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H02 OCA]. | | 1H02 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1H02 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb52_1.html Growth Hormone]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H02 OCA]. |
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| ==Reference==
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| 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:[http://www.ncbi.nlm.nih.gov/pubmed/12135360 12135360]
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| [[Category: Growth Hormone]] | | [[Category: Growth Hormone]] |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
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| [[Category: Insulin family]] | | [[Category: Insulin family]] |
| [[Category: Plasma]] | | [[Category: Plasma]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:14:23 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:26:55 2008'' |