3SD4

Crystal structure of the first Tudor domain of human PHF20

Summary for 3SD4

• Entry DOI: 10.2210/pdb3sd4/pdb
• Related: 3P8D
• Descriptor: PHD finger protein 20 (2 entities in total)
• Functional Keywords: tudor domain, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 17075.13

Authors

Cui, G.,Botuyan, M.V.,Thompson, J.R.,Mer, G. (deposition date: 2011-06-08, release date: 2011-06-22, Last modification date: 2024-04-03)

Primary citation

Cui, G.,Park, S.,Badeaux, A.I.,Kim, D.,Lee, J.,Thompson, J.R.,Yan, F.,Kaneko, S.,Yuan, Z.,Botuyan, M.V.,Bedford, M.T.,Cheng, J.Q.,Mer, G.
PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.
Nat.Struct.Mol.Biol., 19:916-924, 2012

PubMed Abstract: PHF20 is a multidomain protein and subunit of a lysine acetyltransferase complex that acetylates histone H4 and p53 but whose function is unclear. Using biochemical, biophysical and cellular approaches, we determined that PHF20 is a direct regulator of p53. A Tudor domain in PHF20 recognized p53 dimethylated at Lys370 or Lys382 and a homodimeric form of this Tudor domain could associate with the two dimethylated sites on p53 with enhanced affinity, indicating a multivalent interaction. Association with PHF20 promotes stabilization and activation of p53 by diminishing Mdm2-mediated p53 ubiquitylation and degradation. PHF20 contributes to upregulation of p53 in response to DNA damage, and ectopic expression of PHF20 in different cell lines leads to phenotypic changes that are hallmarks of p53 activation. Overall our work establishes that PHF20 functions as an effector of p53 methylation that stabilizes and activates p53.

PubMed: 22864287
DOI: 10.1038/nsmb.2353

Experimental method

X-RAY DIFFRACTION (1.928 Å)