Solution structure of the RWD domain of the mouse GCN2 protein

Nobukazu Nameki, Misao Yoneyama, Seizo Koshiba, Naoya Tochio, Makoto Inoue, Eiko Seki, Takayoshi Matsuda, Yasuko Tomo, Takushi Harada, Kohei Saito, Naohiro Kobayashi, Takashi Yabuki, Masaaki Aoki, Emi Nunokawa, Natsuko Matsuda, Noriko Sakagami, Takaho Terada, Mikako Shirouzu, Mayumi Yoshida, Hiroshi HirotaTakashi Osanai, Akiko Tanaka, Takahiro Arakawa, Piero Carninci, Jun Kawai, Yoshihide Hayashizaki, Kengo Kinoshita, Peter Güntert, Takanori Kigawa, Shigeyuki Yokoyama

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60 Citations (Scopus)


GCN2 is the α-subunit of the only translation initiation factor (eIF2α) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. In this study, we determined the solution structure of the mouse GCN2 RWD domain using NMR spectroscopy. The structure forms an α + β sandwich fold consisting of two layers: a four-stranded antiparallel β-sheet, and three side-by-side α-helices, with an αββββα α topology. A characteristic YPXXXP motif, which always occurs in RWD domains, forms a stable loop including three consecutive β-turns that overlap with each other by two residues (triple β-turn). As putative binding sites with GCN1, a structure-based alignment allowed the identification of several surface residues in α-helix 3 that are characteristic of the GCN2 RWD domains. Despite the apparent absence of sequence similarity, the RWD structure significantly resembles that of ubiquitin-conjugating enzymes (E2s), with most of the structural differences in the region connecting β-strand 4 and α-helix 3. The structural architecture, including the triple β-turn, is fundamentally common among various RWD domains and E2s, but most of the surface residues on the structure vary. Thus, it appears that the RWD domain is a novel structural domain for protein-binding that plays specific roles in individual RWD-containing proteins.

Original languageEnglish
Pages (from-to)2089-2100
Number of pages12
JournalProtein Science
Issue number8
Publication statusPublished - 2004 Aug


  • GI domain
  • Hydrogen bond network
  • NMR
  • Protection factor
  • Protein structure


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