Structural analysis of Ca²⁺-binding pocket of synaptotagmin 5 C2A domain

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• 作者：Xiaoting Qiu^a ; ^b ; ^c ; ^d ; Junyi Ge^a ; ^b ; Yongxiang Gao^c ; ^d ; Maikun Teng^c ; ^d ; ^{mkteng@ustc.edu.cn} ; Liwen Niu^c ; ^d ; ^{lwniu@ustc.edu.cn}
• 关键词：Synaptotagmin C2 domain ; Ca2+-binding pocket ; Ca2+-binding mechanism
• 刊名：International Journal of Biological Macromolecules
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：95
• 期：Complete
• 页码：946-953
• 全文大小：2533 K
• 卷排序：95

文摘

Synaptotagmins constitute a family of multifunctional integral membrane proteins found predominantly on vesicles in neural and endocrine tissues. 17 isoforms of synaptotagmin family in mammals have been identified, 7 isoforms among them are known to be able to bind Ca2+ via their C2 domains. This study presents the crystal structure of the first C2 domain (C2A domain) of synaptotagmin 5 complexed with Ca2+ at 1.90 Å resolution. Comparison of the Ca2+-binding pocket of synaptotagmin 5 C2A domain with other synaptotagmin C2 domains demonstrated that a serine residue locating at Ca2+-binding loop probably responsible to the conformational variation of Ca2+-binding pocket, and thus impacts the Ca2+-binding mechanism of C2 domain, which is verified by structural analysis of the serine mutant and Ca2+-binding assays via isothermal titration calorimetry. Alteration of Ca2+-binding mechanism might be correlated with different Ca2+ response rates of synaptotagmins, which is the basis of the functions of synaptotagmins in regulating various types of Ca2+-triggered vesicle-membrane fusion processes.