Solution structure of the PWWP domain of the hepatoma-derived growth factor family

Nobukazu Nameki, Naoya Tochio, Seizo Koshiba, Makoto Inoue, Takashi Yabuki, Masaaki Aoki, Eiko Seki, Takayoshi Matsuda, Yukiko Fujikura, Miyuki Saito, Masaomi Ikari, Megumi Watanabe, Takaho Terada, Mikako Shirouzu, Mayumi Yoshida, Hiroshi Hirota, Akiko Tanaka, Yoshihide Hayashizaki, Peter Güntert, Takanori KigawaShigeyuki Yokoyama

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 β-barrel with a PWWP-specific long loop connecting β2 and β3 (PR-loop), followed by a helical region including two α-helices. Its structure was found to have a characteristic solvent-exposed hydrophobic cavity, which is composed of an abundance of aromatic residues in the β1/β2 loop (β-β arch) and the β3/β4 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.

Original languageEnglish
Pages (from-to)756-764
Number of pages9
JournalProtein Science
Volume14
Issue number3
DOIs
Publication statusPublished - 2005 Mar 1
Externally publishedYes

Keywords

  • Cavity
  • HATH region
  • HDGF
  • NMR
  • PR-loop
  • Protein structure
  • β-β arch

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Nameki, N., Tochio, N., Koshiba, S., Inoue, M., Yabuki, T., Aoki, M., Seki, E., Matsuda, T., Fujikura, Y., Saito, M., Ikari, M., Watanabe, M., Terada, T., Shirouzu, M., Yoshida, M., Hirota, H., Tanaka, A., Hayashizaki, Y., Güntert, P., ... Yokoyama, S. (2005). Solution structure of the PWWP domain of the hepatoma-derived growth factor family. Protein Science, 14(3), 756-764. https://doi.org/10.1110/ps.04975305