The catalytic subunit of the SWR1 remodeler is a histone chaperone for the H2A.Z-H2B dimer

Mol Cell. 2014 Feb 6;53(3):498-505. doi: 10.1016/j.molcel.2014.01.010.

Abstract

Histone variant H2A.Z-containing nucleosomes exist at most eukaryotic promoters and play important roles in gene transcription and genome stability. The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. How SWR1 catalyzes the replacement reaction is largely unknown. Here, we determined the crystal structure of the N-terminal region (599-627) of the catalytic subunit Swr1, termed Swr1-Z domain, in complex with the H2A.Z-H2B dimer at 1.78 Å resolution. The Swr1-Z domain forms a 310 helix and an irregular chain. A conserved LxxLF motif in the Swr1-Z 310 helix specifically recognizes the αC helix of H2A.Z. Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / physiology
  • Amino Acid Sequence
  • Chromatin Assembly and Disassembly / genetics
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Dimerization
  • Histones / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / physiology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / physiology
  • X-Ray Diffraction

Substances

  • Histones
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphatases
  • Swr1 protein, S cerevisiae

Associated data

  • PDB/4M6B