1l3e: Difference between revisions
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==Overview== | ==Overview== | ||
Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive | Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1 alpha. CH1 has a triangular geometry composed of four alpha-helices with three intervening Zn(2+)-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1 alpha C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1 alpha, and shows how HIF-1 alpha transactivation is regulated by asparagine hydroxylation. | ||
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Eck, M | [[Category: Eck, M J.]] | ||
[[Category: Freedman, S | [[Category: Freedman, S J.]] | ||
[[Category: Kung, A | [[Category: Kung, A L.]] | ||
[[Category: Livingston, D | [[Category: Livingston, D M.]] | ||
[[Category: Poy, F.]] | [[Category: Poy, F.]] | ||
[[Category: Sun, Z | [[Category: Sun, Z J.]] | ||
[[Category: Wagner, G.]] | [[Category: Wagner, G.]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
''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 13:40:52 2008'' | ||
Revision as of 11:40, 21 February 2008
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NMR Structures of the HIF-1alpha CTAD/p300 CH1 Complex
Overview
Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1 alpha. CH1 has a triangular geometry composed of four alpha-helices with three intervening Zn(2+)-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1 alpha C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1 alpha, and shows how HIF-1 alpha transactivation is regulated by asparagine hydroxylation.
Disease
Known diseases associated with this structure: Colorectal cancer OMIM:[602700], Rubinstein-Taybi syndrome OMIM:[602700]
About this Structure
1L3E is a Protein complex structure of sequences from Homo sapiens with ZN as ligand. Known structural/functional Sites: Zn1, Zn2 and Zn3. Full crystallographic information is available from OCA.
Reference
Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha., Freedman SJ, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ, Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5367-72. PMID:11959990
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