title: Structure of the histone chaperone ASF1 bound to the histone H3 C-terminal helix and functional insights.
abstract: Asf1 is a histone chaperone that favors histone H3/H4 assembly and disassembly. We solved the structure of the conserved domain of human ASF1A in complex with the C-terminal helix of histone H3 using nuclear magnetic resonance spectroscopy. This structure is fully compatible with an association of ASF1 with the heterodimeric form of histones H3/H4. In our model, ASF1 substitutes for the second H3/H4 heterodimer that is normally found in heterotetrameric H3/H4 complexes. This result constitutes an essential step in the fundamental understanding of the mechanisms of nucleosome assembly by histone chaperones. Point mutations that perturb the Asf1/histone interface were designed from the structure. The decreased binding affinity of the Asf1-H3/H4 complex correlates with decreased levels of H3-K56 acetylation and phenotypic defects in vivo.
authors.affiliation: Institut de Biologie et de Technologie de Saclay, Commissariat à l'Energie Atomique/Saclay, F-91191 Gif-sur-Yvette Cedex, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Agez
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Raphaël
authors.initials: R
authors.lastname: Guerois
authors.forename: Carine
authors.initials: C
authors.lastname: van Heijenoort
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Thuret
authors.forename: Carl
authors.initials: C
authors.lastname: Mann
authors.forename: Francoise
authors.initials: F
authors.lastname: Ochsenbein
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics; D002478:Cells, Cultured; D019281:Dimerization; D006657:Histones / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics; D017354:Point Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: C491641:ASF1A protein, human; D018797:Cell Cycle Proteins; D006657:Histones; D018832:Molecular Chaperones