Solution structure of histone chaperone ANP32B: interaction with core histones H3-H4 through its acidic concave domain.
Eukaryotic gene expression is regulated by histone deposition onto and eviction from nucleosomes, which are mediated by several chromatin-modulating factors. Among them, histone chaperones are key factors that facilitate nucleosome assembly. Acidic nuclear phosphoprotein 32B (ANP32B) belongs to the ANP32 family, which shares N-terminal leucine-rich repeats (LRRs) and a C-terminal variable anionic region. The C-terminal region functions as an inhibitor of histone acetylation, but the functional roles of the LRR domain in chromatin regulation have remained elusive. Here, we report that the LRR domain of ANP32B possesses histone chaperone activity and forms a curved structure with a parallel beta-sheet on the concave side and mostly helical elements on the convex side. Our analyses revealed that the interaction of ANP32B with the core histones H3-H4 occurs on its concave side, and both the acidic and hydrophobic residues that compose the concave surface are critical for histone binding. These results provide a structural framework for understanding the functional mechanisms of acidic histone chaperones.
RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Naoya
N
Tochio
Takashi
T
Umehara
Yoshiko
Y
Munemasa
Toru
T
Suzuki
Shin
S
Sato
Kengo
K
Tsuda
Seizo
S
Koshiba
Takanori
T
Kigawa
Ryozo
R
Nagai
Shigeyuki
S
Yokoyama
D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D056488:Histone Chaperones / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D012996:Solutions / Q000494:pharmacology
C490341:ANP32B protein, human; D024342:Amino Acids, Acidic; D056488:Histone Chaperones; D006657:Histones; D009687:Nuclear Proteins; D012996:Solutions