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HMGB1-facilitated p53 DNA binding occurs via HMG-box/p53 transactivation domain interaction and is regulated by the acidic tailHMGB1-facilitated p53 DNA binding occurs via HMG-box/p53 transactivation domain interaction and is regulated by the acidic tail
Structural highlights
FunctionHMGB1_HUMAN DNA binding proteins that associates with chromatin and has the ability to bend DNA. Binds preferentially single-stranded DNA. Involved in V(D)J recombination by acting as a cofactor of the RAG complex. Acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS). Heparin-binding protein that has a role in the extension of neurite-type cytoplasmic processes in developing cells (By similarity). Publication Abstract from PubMedFacilitated binding of p53 to DNA by high mobility group B1 (HMGB1) may involve interaction between the N-terminal region of p53 and the high mobility group (HMG) boxes, as well as HMG-induced bending of the DNA. Intramolecular shielding of the boxes by the HMGB1 acidic tail results in an unstable complex with p53 until the tail is truncated to half its length, at which point the A box, proposed to be the preferred binding site for p53(1-93), is exposed, leaving the B box to bind and bend DNA. The A box interacts with residues 38-61 (TAD2) of the p53 transactivation domain. Residues 19-26 (TAD1) bind weakly, but only in the context of p53(1-93) and not as a free TAD1 peptide. We have solved the structure of the A-box/p53(1-93) complex by nuclear magnetic resonance spectroscopy. The incipient amphipathic helix in TAD2 recognizes the concave DNA-binding face of the A box and may be acting as a single-stranded DNA mimic. HMGB1-Facilitated p53 DNA Binding Occurs via HMG-Box/p53 Transactivation Domain Interaction, Regulated by the Acidic Tail.,Rowell JP, Simpson KL, Stott K, Watson M, Thomas JO Structure. 2012 Dec 5;20(12):2014-24. doi: 10.1016/j.str.2012.09.004. Epub 2012, Oct 11. PMID:23063560[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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