1h02: Difference between revisions
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==Overview== | ==Overview== | ||
Human insulin-like growth factors I and II (hIGF-I, hIGF-II) are potent | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bree, F | [[Category: Bree, F M.De.]] | ||
[[Category: Brzozowski, A | [[Category: Brzozowski, A M.]] | ||
[[Category: Dauter, Z.]] | [[Category: Dauter, Z.]] | ||
[[Category: Dodson, E | [[Category: Dodson, E J.]] | ||
[[Category: Dodson, G | [[Category: Dodson, G G.]] | ||
[[Category: Murshudov, G.]] | [[Category: Murshudov, G.]] | ||
[[Category: Turkenburg, J | [[Category: Turkenburg, J P.]] | ||
[[Category: Verma, C.]] | [[Category: Verma, C.]] | ||
[[Category: C15]] | [[Category: C15]] | ||
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[[Category: plasma]] | [[Category: plasma]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:55:57 2008'' | ||
Revision as of 13:56, 21 February 2008
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HUMAN INSULIN-LIKE GROWTH FACTOR; SRS DARESBURY DATA
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Growth retardation with deafness and mental retardation due to IGF1 deficiency OMIM:[147440]
About this StructureAbout this Structure
1H02 is a Single protein structure of sequence from Homo sapiens with as ligand. The following page contains interesting information on the relation of 1H02 with [Growth Hormone]. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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
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