PDBsum entry 2mwp

Transcription/antitumor protein

PDB id: 2mwp

Contents

Protein chains

123 a.a.

12 a.a.

PDB id:

2mwp

Name:

Transcription/antitumor protein

Title:

Solution structure of 53bp1 tandem tudor domains in complex with a p53k382me2 peptide

Structure:

Tumor suppressor p53-binding protein 1. Chain: a. Fragment: tudor-like region residues 1484-1603. Synonym: 53bp1, p53-binding protein 1, p53bp1. Engineered: yes. Cellular tumor antigen p53. Chain: b. Fragment: DNA-binding repression region residues 376-387. Synonym: p53k382me2, antigen ny-co-13, phosphoprotein p53, tumor

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tp53bp1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

NMR struc:

20 models

Authors:

G.Cui,M.V.Botuyan,G.Mer

Key ref:

Q.Tong et al. (2015). Structural plasticity of methyllysine recognition by the tandem tudor domain of 53BP1. Structure, 23, 312-321. PubMed id: 25579814 DOI: 10.1016/j.str.2014.11.013

Date:

15-Nov-14 Release date: 10-Dec-14

Protein chain

Q12888  (TP53B_HUMAN) -  TP53-binding protein 1 from Homo sapiens

Seq: 1972 a.a.

Struc: 123 a.a.*

Protein chain

P04637  (P53_HUMAN) -  Cellular tumor antigen p53 from Homo sapiens

Seq: 393 a.a.

Struc: 12 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1016/j.str.2014.11.013

Structure 23:312-321 (2015)

PubMed id: 25579814

Structural plasticity of methyllysine recognition by the tandem tudor domain of 53BP1.

Q.Tong, G.Cui, M.V.Botuyan, S.B.Rothbart, R.Hayashi, C.A.Musselman, N.Singh, E.Appella, B.D.Strahl, G.Mer, T.G.Kutateladze.

ABSTRACT

p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 cofactor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage.