| Project/Area Number |
10179104
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Hokkaido University (1999-2001)
Tokyo Metropolitan Organization for Medical Research (1998) |
|---|
Principal Investigator |
INAGAKI Fuyuhiko Hokkaido University, professor, 大学院・薬学研究科, 教授 (70011757)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUKITA Shoichiro Kyoto University, professor, 大学院・医学研究科, 教授 (50155347)
YAMAMOTO Tadashi Tokyo University, professor, 医科学研究所, 教授 (40134621)
TAKENAWA Tadaomi Tokyo University, professor, 医科学研究所, 教授 (40101315)
KOHDA Daisuke Kyushu University, professor, 生体防御医学研究所・バイオサイエンス研究, 教授 (80186618)
HAKOSHIMA Toshio Nara Institute of Science and Technology, professor, バイオサイエンス研究科, 教授 (00164773)
嶋田 一夫 東京大学, 大学院・薬学系研究科, 教授 (70196476)
貝淵 弘三 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (00169377)
|
|---|
| Project Period (FY) |
1998 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥131,800,000 (Direct Cost: ¥131,800,000)
Fiscal Year 2001: ¥30,700,000 (Direct Cost: ¥30,700,000)
Fiscal Year 2000: ¥34,600,000 (Direct Cost: ¥34,600,000)
Fiscal Year 1999: ¥31,900,000 (Direct Cost: ¥31,900,000)
Fiscal Year 1998: ¥34,600,000 (Direct Cost: ¥34,600,000)
|
|---|
| Keywords | Vav / SH3 / Grb2 / praline rich region / tertiary structure IP3 / radixin / IP3 / PTB様ドメイン / Vav-nSH3 / PRR / Grb2-cSH3 / バキュロウィルス / 多核体病ウィルス / Rho / N-WASP / NMR / X線結晶構造解析 / タイトジャンクション / 好中級活性酸素発生系 / PBI / PB2 / Neurop |
|---|
| Research Abstract |
Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Srchomology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal strucuture of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS β-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.
|
