An acetyl-methyl switch drives a conformational change in p53.
作者： Qiong Tong , Sharlyn J. Mazur , Hector Rincon-Arano , Scott B. Rothbart , Dmitry M. Kuznetsov
DOI: 10.1016/J.STR.2014.12.010
关键词:
摘要: Individual posttranslational modifications (PTMs) of p53 mediate diverse p53-dependent responses; however, much less is known about the combinatorial action adjacent modifications. Here, we describe crosstalk between early DNA damage response mark p53K382me2 and surrounding PTMs that modulate binding cofactors, including 53BP1 p300. The 1.8 A resolution crystal structure tandem Tudor domain (TTD) of in complex with peptide acetylated at K381 dimethylated K382 (p53K381acK382me2) reveals dual PTM induces a conformational change p53. α-helical fold p53K381acK382me2 positions side chains R379, K381ac, K382me2 to interact TTD concurrently, reinforcing modular design double mimetics. Biochemical nuclear magnetic resonance analyses show other PTMs, phosphorylation serine/threonine residues p53, affect association TTD. Our findings suggest novel PTM-driven conformation switch-like mechanism may regulate interactions partners.
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