Crystal structure and regulation of Fer

2010 Fiscal Year Final Research Report

• Project/Area Number: 20570194
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MASUDA Michitaka 独立行政法人国立循環器病研究センター, 細胞生物学部, 室長 (00190364)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Soichi 独立行政法人国立循環器病研究センター, 心臓整理機能部, 室長 (80332279) ; BEN Ammar Youssef 富士フイルム, 解析技術センター, 研究員 (90463273)
• Project Period (FY): 2008 – 2010
• Keywords: 生体膜 / バードメイン / チロシンキナーゼ / タンパク質構造

Research Abstract

Formation of tubes or buds from a flat membrane is a widely spread feature of the membrane shape change during the vesicular transport and the organelle morphogenesis. The BAR domain dimers exhibit curved banana shapes and appear to be suitable modules for this process. However, the BAR domains of Fer/Fes kinases, which have the coiled-coil domains just C-terminal of the BAR domain, show exceptionally low levels of membrane tubulation. We determined the crystal structure of the N-terminal half of Fer containing the BAR and the coiled-coil domains. They unite together into a banana-shape dimer. The membrane-binding surface of the dimer is not hindered by the coiled-coil domains. From comparison of the known BAR dimer structures, we have found out that there are two conserved residues on the non-membrane binding surfaces other than the Fer/Fes BAR domains. When these two residues of Fer were mutated into the conserved residues, the mutant Fer showed effective membrane tubulation activity. This result provides a new insight into the molecular mechanism for membrane deformation by the BAR domains.

Research Products

• [Journal Article] Structural characteristics of BAR domain superfamily to sculpt the membrane (2010)
  • Author(s): Masuda M. and Mochizuki N
  • Journal Title: Seminars in Cell & Developmental Biology Volume: 21 Pages: 391-398
  • Peer Reviewed
• [Journal Article] Mechanism of inhibition of tumor angiogenesis by beta-hydroxyisovalerylshikonin (2009)
  • Author(s): Komi Y, Suzuki Y, Shimamura M, Kajimoto S, Nakajo S, Masuda M, Shibuya M, Itabe H, Shimokado K, Oettgen P, Nakaya K, and Kojima S
  • Journal Title: Cancer Science Volume: 100 Pages: 269-277
  • Peer Reviewed
• [Remarks]
  • URL: http://www.ncvc.go.jp/res/index.html