First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.
1l8c
From Proteopedia
STRUCTURAL BASIS FOR HIF-1ALPHA/CBP RECOGNITION IN THE CELLULAR HYPOXIC RESPONSE
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1L8C is a 2 chains structure with sequences from Homo sapiens and Mus musculus. The February 2010 RCSB PDB Molecule of the Month feature on Enhanceosome by David Goodsell is 10.2210/rcsb_pdb/mom_2010_2. Full experimental information is available from OCA.
Reference
- Dames SA, Martinez-Yamout M, De Guzman RN, Dyson HJ, Wright PE. Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5271-6. PMID:11959977 doi:10.1073/pnas.082121399
Page seeded by OCA on Wed Jan 20 22:16:11 2010
