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Title
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A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding.
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Authors
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B.A.Davletov,
T.C.Südhof.
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Ref.
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J Biol Chem, 1993,
268,
26386-26390.
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PubMed id
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Abstract
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Synaptotagmin I is a Ca(2+)- and phospholipid-binding protein of synaptic
vesicles with an essential function in neurotransmission. Ca2+/phospholipid
binding by synaptotagmin I may be mediated by its C2 domains, sequence motifs
that have been implicated in the Ca2+ regulation of a variety of proteins.
However, it is currently unknown if C2 domains are sufficient for
Ca2+/phospholipid binding or if they even directly participate in
Ca2+/phospholipid binding. In order to address this question, we have studied
the Ca2+/phospholipid-binding properties of the first C2 domain of synaptotagmin
I. Our results show that this C2 domain by itself binds Ca2+ and phospholipids
with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits
strong positive cooperativity. The C2 domain is specific for negatively charged
phospholipids and for those divalent cations that are known to stimulate
synaptic vesicle exocytosis (Ca2+ > Sr2+, Ba2+ >>> Mg2+). These
studies establish that C2 domains can serve as independently folding
Ca2+/phospholipid-binding domains. Furthermore, the cation specificity and the
cooperativity of Ca2+ binding by the C2 domain from synaptotagmin I support a
role for this protein in mediating the Ca2+ signal in neurotransmitter release.
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