1l8c
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="1l8c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l8c" /> '''STRUCTURAL BASIS FOR HIF-1ALPHA/CBP RECOGNI...)
Next diff →
Revision as of 15:51, 12 November 2007
|
STRUCTURAL BASIS FOR HIF-1ALPHA/CBP RECOGNITION IN THE CELLULAR HYPOXIC RESPONSE
Overview
The cellular response to low tissue oxygen concentrations is mediated by, the hypoxia-inducible transcription factor HIF-1. Under hypoxic, conditions, HIF-1 activates transcription of critical adaptive genes by, recruitment of the general coactivators CBP/p300 through interactions with, its alpha-subunit (Hif-1 alpha). Disruption of the Hif-1 alpha/p300, interaction has been linked to attenuation of tumor growth. To delineate, the structural basis for this interaction, we have determined the solution, structure of the complex between the carboxy-terminal activation domain, (CAD) of Hif-1 alpha and the zinc-binding TAZ1 (CH1) motif of cyclic-AMP, response element binding protein (CREB) binding protein (CBP). Despite the, overall similarity of the TAZ1 structure to that of the TAZ2 (part of the, CH3) domain of CBP, differences occur in the packing of helices that can, account for differences in specificity. The unbound CAD is intrinsically, disordered and remains relatively extended upon binding, wrapping almost, entirely around the TAZ1 domain in a groove through much of its surface., Three short helices are formed upon binding, stabilized by intermolecular, interactions. The Asn-803 side chain, which functions as a hypoxic switch, is located on the second of these helices and is buried in the molecular, interface. The third helix of the Hif-1 alpha CAD docks in a deep, hydrophobic groove in TAZ1, providing extensive intermolecular hydrophobic, interactions that contribute to the stability of the complex. The, structure of this complex provides new insights into the mechanism through, which Hif-1 alpha recruits CBP/p300 in response to hypoxia.
About this Structure
1L8C is a Protein complex structure of sequences from Homo sapiens and Mus musculus with ZN as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response., Dames SA, Martinez-Yamout M, De Guzman RN, Dyson HJ, Wright PE, Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5271-6. PMID:11959977
Page seeded by OCA on Mon Nov 12 17:57:36 2007
