PDBsum entry 3lgl

Cell cycle

PDB id

3lgl

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Contents

			Protein chain

					119 a.a. *

			Ligands

					MLY


					PGE


					SO4

			Waters ×125

* Residue conservation analysis

PDB id:

3lgl

Links

Name:

Cell cycle

Title:

Crystal structure of the 53bp1 tandem tudor domain in complex with p53k382me2

Structure:

Tumor suppressor p53-binding protein 1. Chain: a. Fragment: tandem tudor domains (resiudes 1484-1603). Synonym: p53-binding protein 1, p53bp1, 53bp1. Engineered: yes. Dimethylated p53 lysine 382 peptide. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tp53bp1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized

Resolution:

1.60Å

R-factor:

0.209

R-free:

0.251

Authors:

S.Roy,T.G.Kutateladze

Key ref:

S.Roy et al. (2010). Structural insight into p53 recognition by the 53BP1 tandem Tudor domain. J Mol Biol, 398, 489-496. PubMed id: 20307547

Date:

20-Jan-10

Release date:

23-Mar-10

PROCHECK

	Headers

	References

Protein chain

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

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					1972 a.a. 119 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

	J Mol Biol 398:489-496 (2010)
PubMed id: 20307547

Structural insight into p53 recognition by the 53BP1 tandem Tudor domain.
S.Roy, C.A.Musselman, I.Kachirskaia, R.Hayashi, K.C.Glass, J.C.Nix, O.Gozani, E.Appella, T.G.Kutateladze.

ABSTRACT

The tumor suppressor p53 and the DNA repair factor 53BP1 (p53 binding protein 1) regulate gene transcription and responses to genotoxic stresses. Upon DNA damage, p53 undergoes dimethylation at Lys382 (p53K382me2), and this posttranslational modification is recognized by 53BP1. The molecular mechanism of nonhistone methyl-lysine mark recognition remains unknown. Here we report a 1. 6-A-resolution crystal structure of the tandem Tudor domain of human 53BP1 bound to a p53K382me2 peptide. In the complex, dimethylated Lys382 is restrained by a set of hydrophobic and cation-pi interactions in a cage formed by four aromatic residues and an aspartate of 53BP1. The signature HKKme2 motif of p53, which defines specificity, is identified through a combination of NMR resonance perturbations, mutagenesis, measurements of binding affinities and docking simulations, and analysis of the crystal structures of 53BP1 bound to p53 peptides containing other dimethyl-lysine marks, p53K370me2 (p53 dimethylated at Lys370) and p53K372me2 (p53 dimethylated at Lys372). Binding of the 53BP1 Tudor domain to p53K382me2 may facilitate p53 accumulation at DNA damage sites and promote DNA repair as suggested by chromatin immunoprecipitation and DNA repair assays. Together, our data detail the molecular mechanism of p53-53BP1 association and provide the basis for deciphering the role of this interaction in the regulation of p53 and 53BP1 functions.

Literature references that cite this PDB file's key reference

PubMed id

Reference

23142980

C.A.Musselman, N.Avvakumov, R.Watanabe, C.G.Abraham, M.E.Lalonde, Z.Hong, C.Allen, S.Roy, J.K.Nuñez, J.Nickoloff, C.A.Kulesza, A.Yasui, J.Côté, and T.G.Kutateladze (2012).
Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.

Nat Struct Mol Biol, 19, 1266-1272.

PDB code:

4hcz

22864287

G.Cui, S.Park, A.I.Badeaux, D.Kim, J.Lee, J.R.Thompson, F.Yan, S.Kaneko, Z.Yuan, M.V.Botuyan, M.T.Bedford, J.Q.Cheng, and G.Mer (2012).
PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.

Nat Struct Mol Biol, 19, 916-924.

PDB codes:

2ldm 3p8d 3sd4

21071205

G.Schreiber, and A.E.Keating (2011).
Protein binding specificity versus promiscuity.

Curr Opin Struct Biol, 21, 50-61.

21361779

S.T.Al Rashid, S.M.Harding, C.Law, C.Coackley, and R.G.Bristow (2011).
Protein-protein interactions occur between p53 phosphoforms and ATM and 53BP1 at sites of exogenous DNA damage.

Radiat Res, 175, 588-598.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.