Structural study for the recognition mechanism of the target protein by a novel calcium sensor
| Project/Area Number |
17570095
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Yokohama City University |
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Principal Investigator |
SHIMIZU Toshiyuki Yokohama City University, International Graduate School of Arts and Sciences, Associate Professor, 国際総合科学研究科, 准教授 (30273858)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | CHP / EF-hand / calcium / X-ray analysis / NHE1 / calcineurin / DRAK2 |
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| Research Abstract |
Calcium ion plays significant role as a second messenger of intra cellular signaling in eukaryote. Rising concentration of intra cellar calcium is arisen by afflux of extra cellar calcium mediated by calcium channel and release of calcium from endoplasmic reticulum. Calcium binding protein binds to calcium and causes conformation change to modify down stream target molecules when intra cellar calcium rises.
CHP1 is comprised of 195 amino acids and shows substantial sequence similarity to the regulatory B subunit of calcineurin (CNB). Based on amino acid sequence CHP1 has 4 EF-hands (EF-1-4) that is known as calcium binding motif and N-myristoylation motif on its N-terminal..
CHP1 was also identified as a protein that interacts with intra cellar juxta-membrane region of Na+/H+ exchanger 1 (NHE1). CHP1 is essential for NHEls activity, and CHP1 binding defective mutant of NHE1 show a marked acidic shift of intra cellar pH. Furthermore, a mutant which displays lacking calcium-binding affinit
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y, also has a significantly reduced Na+/H+ exchange activity. Furthermore recent study reveals that CHP1 binds to DAPK related apoptosis inducing kinase 2 (DRAK2) and inhibits its kinase activity. CHP1 significantly reduced (〜85% inhibition) the kinase activity of DRAK2 for both autophosphorylation and phsphorylation of exogenous substrate. DRAK2 is a Ser/Thr kinase consisting of 371 amino acids and mainly consists of kinase domain (residues 33-293) The enzyme activity of some members of DAP kinase family is regulated via binding of calmodulin to a calmodulin binding region It is interesting that calcium and CHP1 negatively regulate the kinase activity of DRAK2 required for apoptotic induction.
CHP1 binding regions of NHE1 and DRAK2 have low similarity, so CHP1 may interact with multiple target on multiple manner. Despite the great importance of multiple intracellular functions of CHP1, no structural information of CHP1 has been obtained. In this study we performed X-ray crystallographic analysis of CHP1 to clarify CHP1s target recognition mechanism. We also perform crystallization of DRAK2. Less
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Report
(3 results)
Research Products
(23 results)
