Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1

Qiong Tong, Gaofeng Cui, Maria Victoria Botuyan, Scott B. Rothbart, Ryo Hayashi, Catherine A. Musselman, Namit Singh, Ettore Appella, Brian D. Strahl, Georges Mer, Tatiana G. Kutateladze

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)312-321
Number of pages10
JournalStructure
Volume23
Issue number2
DOIs
StatePublished - Feb 3 2015

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Post Translational Protein Processing
Peptides
Histones
DNA Damage
Tudor Domain

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Tong, Q., Cui, G., Botuyan, M. V., Rothbart, S. B., Hayashi, R., Musselman, C. A., ... Kutateladze, T. G. (2015). Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1. Structure, 23(2), 312-321. https://doi.org/10.1016/j.str.2014.11.013

Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1. / Tong, Qiong; Cui, Gaofeng; Botuyan, Maria Victoria; Rothbart, Scott B.; Hayashi, Ryo; Musselman, Catherine A.; Singh, Namit; Appella, Ettore; Strahl, Brian D.; Mer, Georges; Kutateladze, Tatiana G.

In: Structure, Vol. 23, No. 2, 03.02.2015, p. 312-321.

Research output: Contribution to journalArticle

Tong, Q, Cui, G, Botuyan, MV, Rothbart, SB, Hayashi, R, Musselman, CA, Singh, N, Appella, E, Strahl, BD, Mer, G & Kutateladze, TG 2015, 'Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1', Structure, vol. 23, no. 2, pp. 312-321. https://doi.org/10.1016/j.str.2014.11.013
Tong Q, Cui G, Botuyan MV, Rothbart SB, Hayashi R, Musselman CA et al. Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1. Structure. 2015 Feb 3;23(2):312-321. https://doi.org/10.1016/j.str.2014.11.013
Tong, Qiong ; Cui, Gaofeng ; Botuyan, Maria Victoria ; Rothbart, Scott B. ; Hayashi, Ryo ; Musselman, Catherine A. ; Singh, Namit ; Appella, Ettore ; Strahl, Brian D. ; Mer, Georges ; Kutateladze, Tatiana G. / Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1. In: Structure. 2015 ; Vol. 23, No. 2. pp. 312-321.
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