Solution structure of the PWWP domain of the hepatoma-derived growth factor family.
Among the many PWWP-containing proteins, the largest group of homologous proteins is related to hepatoma-derived growth factor (HDGF). Within a well-conserved region at the extreme N-terminus, HDGF and five HDGF-related proteins (HRPs) always have a PWWP domain, which is a module found in many chromatin-associated proteins. In this study, we determined the solution structure of the PWWP domain of HDGF-related protein-3 (HRP-3) by NMR spectroscopy. The structure consists of a five-stranded beta-barrel with a PWWP-specific long loop connecting beta2 and beta3 (PR-loop), followed by a helical region including two alpha-helices. Its structure was found to have a characteristic solvent-exposed hydrophobic cavity, which is composed of an abundance of aromatic residues in the beta1/beta2 loop (beta-beta arch) and the beta3/beta4 loop. A similar ligand binding cavity occurs at the corresponding position in the Tudor, chromo, and MBT domains, which have structural and probable evolutionary relationships with PWWP domains. These findings suggest that the PWWP domains of the HDGF family bind to some component of chromatin via the cavity.
Nameki
Nobukazu
N
RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Tochio
Naoya
N
Koshiba
Seizo
S
Inoue
Makoto
M
Yabuki
Takashi
T
Aoki
Masaaki
M
Seki
Eiko
E
Matsuda
Takayoshi
T
Fujikura
Yukiko
Y
Saito
Miyuki
M
Ikari
Masaomi
M
Watanabe
Megumi
M
Terada
Takaho
T
Shirouzu
Mikako
M
Yoshida
Mayumi
M
Hirota
Hiroshi
H
Tanaka
Akiko
A
Hayashizaki
Yoshihide
Y
Güntert
Peter
P
Kigawa
Takanori
T
Yokoyama
Shigeyuki
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor; D006639:Histidine