Chaperone Nap1 shields histone surfaces used in a nucleosome and can put H2A-H2B in an unconventional tetrameric form

Mol Cell. 2013 Sep 12;51(5):662-77. doi: 10.1016/j.molcel.2013.07.015. Epub 2013 Aug 22.


The histone H2A-H2B heterodimer is an integral component of the nucleosome. The cellular localization and deposition of H2A-H2B into chromatin is regulated by numerous factors, including histone chaperones such as nucleosome assembly protein 1 (Nap1). We use hydrogen-deuterium exchange coupled to mass spectrometry to characterize H2A-H2B and Nap1. Unexpectedly, we find that at low ionic strength, the α helices in H2A-H2B are frequently sampling partially disordered conformations and that binding to Nap1 reduces this conformational sampling. We identify the interaction surface between H2A-H2B and Nap1 and confirm its relevance both in vitro and in vivo. We show that two copies of H2A-H2B bound to a Nap1 homodimer form a tetramer with contacts between H2B chains similar to those in the four-helix bundle structural motif. The organization of the complex reveals that Nap1 competes with histone-DNA and interhistone interactions observed in the nucleosome, thereby regulating the availability of histones for chromatin assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chromatin Assembly and Disassembly
  • DNA, Fungal / metabolism
  • Deuterium Exchange Measurement
  • Histone Chaperones
  • Histones / chemistry
  • Histones / metabolism*
  • Nucleosome Assembly Protein 1 / genetics
  • Nucleosome Assembly Protein 1 / metabolism*
  • Nucleosomes
  • Osmolar Concentration
  • Protein Conformation
  • Protein Folding
  • Protein Multimerization
  • Protein Stability
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Solutions


  • DNA, Fungal
  • Histone Chaperones
  • Histones
  • NAP1 protein, S cerevisiae
  • Nucleosome Assembly Protein 1
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Solutions