7lvs

The CBP TAZ1 Domain in Complex with a CITED2-HIF-1-Alpha Fusion Peptide

spinqualitylabelsall models 7lvs, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lvs is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.02Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CBP_MOUSE Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity). Publication Abstract from PubMed Facilitated dissociation provides a mechanism by which high-affinity complexes can be rapidly disassembled. The negative feedback regulator CITED2 efficiently downregulates the hypoxic response by displacing the hypoxia-inducible transcription factor HIF-1alpha from the TAZ1 domain of the transcriptional coactivators CREB-binding protein (CBP) and p300. Displacement occurs by a facilitated dissociation mechanism involving a transient ternary intermediate formed by binding of the intrinsically disordered CITED2 activation domain to the TAZ1:HIF-1alpha complex. The short lifetime of the intermediate precludes straightforward structural investigations. To obtain insights into the molecular determinants of facilitated dissociation, we model the ternary intermediate by generating a fusion peptide composed of the primary CITED2 and HIF-1alpha binding motifs. X-ray crystallographic and NMR studies of the fusion peptide complex reveal TAZ1-mediated negative cooperativity that results in nearly mutually exclusive binding of specific CITED2 and HIF-1alpha interaction motifs, providing molecular-level insights into the allosteric switch that terminates the hypoxic response. The molecular basis of allostery in a facilitated dissociation process.,Appling FD, Berlow RB, Stanfield RL, Dyson HJ, Wright PE Structure. 2021 Dec 2;29(12):1327-1338.e5. doi: 10.1016/j.str.2021.07.011. Epub , 2021 Sep 13. PMID:34520739 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA