Structure and ligand recognition of the PB1 domain: a novel protein module binding to the PC motif
Hiroaki Terasawa1,2,
Yukiko Noda3,4,
Takashi Ito5,
Hideki Hatanaka1,
Saori Ichikawa6,
Kenji Ogura1,2,7,
Hideki Sumimoto3,4, and
Fuyuhiko Inagaki1,2,7,8
1Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, 2CREST, Japan Science and Technology, 3Department of Molecular and Structural Biology, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, 4Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, 5Division of Genome Biology, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-0934, 6Department of Material and Biological Science, Faculty of Science, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 and 7Department of Structural Biology, Hokkaido University Graduate School of Pharmaceutical Sciences, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan 8Corresponding author at: Department of Structural Biology, Hokkaido University Graduate School of Pharmaceutical Sciences, N12, W6, Kita-ku, Sapporo 060-0812, Japan e-mail: finagaki{at}pharm.hokudai.ac.jp
Abstract:
PB1 domains are novel protein modules capable of binding to target proteins that contain PC motifs. We report here the NMR structure and ligand-binding site of the PB1 domain of the cell polarity establishment protein, Bem1p. In addition, we identify the topology of the PC motif-containing region of Cdc24p by NMR, another cell polarity establishment protein that interacts with Bem1p. The PC motif-containing region is a structural domain offering a scaffold to the PC motif. The chemical shift perturbation experiment and the mutagenesis study show that the PC motif is a major structural element that binds to the PB1 domain. A structural database search reveals close similarity between the Bem1p PB1 domain and the c-Raf1 Ras-binding domain. However, these domains are functionally distinct from each other.
Key Words: Keywords: Bem1p/Cdc24p/NADPH oxidase/p67phox/ p40phox
