Structural and histone binding studies of the chromo barrel domain of TIP60

FEBS Lett. 2018 Apr;592(7):1221-1232. doi: 10.1002/1873-3468.13021. Epub 2018 Mar 25.

Abstract

Tat-interactive protein 60 consists of an N-terminal chromo barrel domain (TIP60-CB) and a C-terminal acetyltransferase domain and acetylates histone and nonhistone proteins in diverse cellular processes. While TIP60-CB is thought to recognize histone tails, molecular details of this interaction remain unclear. Here, we attempted a quantitative analysis of the interaction between the human TIP60-CB and histone peptides, but did not observe any detectable binding by either fluorescence polarization or isothermal titration calorimetry assays. We also determined the crystal structure of the TIP60-CB alone. Analysis of the apo-structure reveals a putative peptide-binding site that might be occluded by the basic side chain of a residue in a unique β hairpin between the two N-terminal strands of the β barrel, leading to the inability of TIP60-CB to bind histones.

Keywords: TIP60; chromo barrel domain; histone methylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Lysine Acetyltransferase 5 / chemistry*
  • Lysine Acetyltransferase 5 / genetics
  • Lysine Acetyltransferase 5 / metabolism
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Protein Domains

Substances

  • Histones
  • Peptides
  • KAT5 protein, human
  • Lysine Acetyltransferase 5

Associated data

  • PDB/2EKO
  • PDB/4QQG
  • PDB/2RJF
  • PDB/2BUD
  • PDB/2K3Y
  • PDB/2F5K
  • PDB/3OA6
  • PDB/1KNE
  • PDB/4A4E
  • PDB/3QJ6
  • PDB/2RO0