title: Solution structure of the PWWP domain of the hepatoma-derived growth factor family.
abstract: 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.
authors.affiliation: RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Nameki
authors.forename: Naoya
authors.initials: N
authors.lastname: Tochio
authors.forename: Seizo
authors.initials: S
authors.lastname: Koshiba
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Yabuki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Aoki
authors.forename: Eiko
authors.initials: E
authors.lastname: Seki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujikura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Masaomi
authors.initials: M
authors.lastname: Ikari
authors.forename: Megumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirota
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Peter
authors.initials: P
authors.lastname: Güntert
authors.forename: Takanori
authors.initials: T
authors.lastname: Kigawa
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: 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
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor; D006639:Histidine