title: Structural analysis of Ca2+-binding pocket of synaptotagmin 5 C2A domain.
abstract: 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 1.90Å 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.
authors: Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, Zhejiang 315211, PR China; School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, PR China; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, PR China.
authors: Xiaoting
authors: X
authors: Qiu
authors: Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, Zhejiang 315211, PR China; School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, PR China.
authors: Junyi
authors: J
authors: Ge
authors: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, PR China.
authors: Yongxiang
authors: Y
authors: Gao
authors: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, PR China. Electronic address: mkteng@ustc.edu.cn.
authors: Maikun
authors: M
authors: Teng
authors: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, PR China. Electronic address: lwniu@ustc.edu.cn.
authors: Liwen
authors: L
authors: Niu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008958:Models, Molecular; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D051381:Rats; D050857:Synaptotagmins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D050857:Synaptotagmins; D002118:Calcium
keywords: Ca(2+)-binding mechanism; Ca(2+)-binding pocket; Synaptotagmin C2 domain