Structural basis for the histone chaperone activity of Asf1.
Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. The structure of the globular domain of Asf1 bound to H3/H4 determined by X-ray crystallography to a resolution of 1.7 Angstroms shows how Asf1 binds the H3/H4 heterodimer, enveloping the C terminus of histone H3 and physically blocking formation of the H3/H4 heterotetramer. Unexpectedly, the C terminus of histone H4 that forms a mini-beta sheet with histone H2A in the nucleosome undergoes a major conformational change upon binding to Asf1 and adds a beta strand to the Asf1 beta sheet sandwich. Interactions with both H3 and H4 were required for Asf1 histone chaperone function in vivo and in vitro. The Asf1-H3/H4 structure suggests a "strand-capture" mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly/assembly that may be used ubiquitously by histone chaperones.
English
Christine M
CM
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045, USA.
Adkins
Melissa W
MW
Carson
Joshua J
JJ
Churchill
Mair E A
ME
Tyler
Jessica K
JK
D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D020868:Gene Silencing; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins