3N5A

Synaptotagmin-7, C2B-domain, calcium bound

Summary for 3N5A

• Entry DOI: 10.2210/pdb3n5a/pdb
• Descriptor: Synaptotagmin-7, CALCIUM ION (3 entities in total)
• Functional Keywords: calcium/phospholipid binding protein, protein transport
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass membrane protein (By similarity): Q9R0N7
• Total number of polymer chains: 1
• Total formula weight: 16116.04

Authors

Tomchick, D.R.,Rizo, J.,Craig, T.K. (deposition date: 2010-05-24, release date: 2010-09-29, Last modification date: 2023-09-06)

Primary citation

Xue, M.,Craig, T.K.,Shin, O.H.,Li, L.,Brautigam, C.A.,Tomchick, D.R.,Sudhof, T.C.,Rosenmund, C.,Rizo, J.
Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7.
Plos One, 5:12544-12544, 2010

PubMed Abstract: Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7). Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 A resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences.

PubMed: 20824061
DOI: 10.1371/journal.pone.0012544

Experimental method

X-RAY DIFFRACTION (1.441 Å)