人體突觸蛋白與肌醇六磷酸之複合物結構探討

莊孟哲

doi:10.6843/NTHU.2012.00017

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人體突觸蛋白與肌醇六磷酸之複合物結構探討

Study on Complex Structure between Human Synaptotagmin I C2B Domain and Inositol Hexakisphosphate

莊孟哲 , Ph.D　　Advisor：余靖　　

英文 DOI： 10.6843/NTHU.2012.00017

核磁共振；突觸結合蛋白；六磷酸肌醇； Nuclear Magnetic Resonance ； Synaptotagmin I ； Inositol hexakisphosphate

Abstract │ Reference (64) │ Times Cited (1) │ Altmetrics

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Abstract
Synaptotagmin I (Syt I) is a synaptic vesicle membrane protein that contains two copies of highly conserved protein kinase C homology regions known as the C2A and C2B domains. The C2A domain binds Ca2+ and the C2B domain binds inositol high polyphosphates (IP4, IP5, and IP6). It has been reported that Ca2+ regulated exocytosis of secretory vesicles is proposed to be activated by Ca2+ binding to the C2A domain and inhibited by inositol polyphosphate binding to the C2B domain. Syt I is also known to be present in neuronal growth cone vesicles. Affinity elution chromatography from the C2 domain of Syt I-immobilized Sepharose using IP6 as the eluent found that several proteins, including an adaptin, specific subunits of the clathrin assembly protein, AP-2 were eluted from the mouse brain. It suggests that inositol high polyphosphate-binding to the C2B domain of Syt I alter the state of protein–protein interaction including the Syt I–AP-2 interaction. Thus, the inositol high polyphosphate may result in the inhibition of events involved in the synaptic vesicle trafficking. In this study, we used NMR to solve the C2B-IP6 3D complex structure. Our data provide new evidence for the hypothesis that the conformational change of C2B binding to IP6 alter the interface of C2B- AP-2. This information will aid in the design of better pharmacological treatments for neurological disorders.

Reference ( 64 ) 〈TOP〉

1. Jahn, R. and Südhof, T. C. (1999) Membrane fusion and exocytosis. Annu Rev Biochem. 68, 863-911.
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2. Augustine, G. J. (2001) How does calcium trigger neurotransmitter release? Curr Opin Neurobiol. 11, 320-3266.
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3. Chapman, E. R., (2002) Synaptotagmin: A Ca2+ that triggers exocytosis? Nat Rev Mol Cell Biol. 3, 498-508.
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5. Matthew, W. D., Tsavaler, L. and Reichardt, L. F., (1981) Identification of a synaptic vesicle-specific membrane protein with a wide distribution in neuronal and neurosecretory tissue. J Cell Biol. 91, 257-69.
連結：
6. Walch-Solimena, C., Takei, K., Marek, K. L., Midyett, K., Südhof, T.C., De Camilli, P. and Jahn, R. (1993) Synaptotagmin: a membrane constituent of neuropeptide-containing large dense-core vesicles. J Neurosci. 13, 3895-3903.
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袁慶齡(2010)。國中生活科技創新教學對學生科技創造力影響之研究－以仿田宮迷你四驅車概念之振動機為例。臺灣師範大學工業教育學系在職進修碩士班學位論文。2010。1-233。

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