title: The catalytic subunit of the SWR1 remodeler is a histone chaperone for the H2A.Z-H2B dimer.
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.
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Jingjun
authors: J
authors: Hong
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Hanqiao
authors: H
authors: Feng
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Feng
authors: F
authors: Wang
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Anand
authors: A
authors: Ranjan
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Jianhong
authors: J
authors: Chen
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors: Jiansheng
authors: J
authors: Jiang
authors: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors: Rodolfo
authors: R
authors: Ghirlando
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors: T Sam
authors: TS
authors: Xiao
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
authors: Carl
authors: C
authors: Wu
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: yawen@helix.nih.gov.
authors: Yawen
authors: Y
authors: Bai
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D019281:Dimerization; D006657:Histones / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000502:physiology; D014961:X-Ray Diffraction
chemical_list: D006657:Histones; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae