Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46.
RbAp46 and RbAp48 (pRB-associated proteins p46 and p48, also known as RBBP7 and RBBP4, respectively) are highly homologous histone chaperones that play key roles in establishing and maintaining chromatin structure. We report here the crystal structure of human RbAp46 bound to histone H4. RbAp46 folds into a seven-bladed beta propeller structure and binds histone H4 in a groove formed between an N-terminal alpha helix and an extended loop inserted into blade six. Surprisingly, histone H4 adopts a different conformation when interacting with RbAp46 than it does in either the nucleosome or in the complex with ASF1, another histone chaperone. Our structural and biochemical results suggest that when a histone H3/H4 dimer (or tetramer) binds to RbAp46 or RbAp48, helix 1 of histone H4 unfolds to interact with the histone chaperone. We discuss the implications of our findings for the assembly and function of RbAp46 and RbAp48 complexes.
Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, UK. nm@mole.bio.cam.ac.uk
Natalia V
NV
Murzina
Xue-Yuan
XY
Pei
Wei
W
Zhang
Mike
M
Sparkes
Jose
J
Vicente-Garcia
J Venkatesh
JV
Pratap
Stephen H
SH
McLaughlin
Tom Rolef
TR
Ben-Shahar
Alain
A
Verreault
Ben F
BF
Luisi
Ernest D
ED
Laue
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D056524:Retinoblastoma-Binding Protein 7; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C490746:RBBP7 protein, human; D056524:Retinoblastoma-Binding Protein 7