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PDBsum entry 5cci
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Endocytosis,exocytosis
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PDB id
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5cci
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Contents |
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62 a.a.
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67 a.a.
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73 a.a.
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64 a.a.
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280 a.a.
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References listed in PDB file
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Key reference
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Title
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Architecture of the synaptotagmin-Snare machinery for neuronal exocytosis.
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Authors
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Q.Zhou,
Y.Lai,
T.Bacaj,
M.Zhao,
A.Y.Lyubimov,
M.Uervirojnangkoorn,
O.B.Zeldin,
A.S.Brewster,
N.K.Sauter,
A.E.Cohen,
S.M.Soltis,
R.Alonso-Mori,
M.Chollet,
H.T.Lemke,
R.A.Pfuetzner,
U.B.Choi,
W.I.Weis,
J.Diao,
T.C.Südhof,
A.T.Brunger.
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Ref.
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Nature, 2015,
525,
62-67.
[DOI no: ]
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PubMed id
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Abstract
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Synaptotagmin-1 and neuronal SNARE proteins have central roles in evoked
synchronous neurotransmitter release; however, it is unknown how they cooperate
to trigger synaptic vesicle fusion. Here we report atomic-resolution crystal
structures of Ca(2+)- and Mg(2+)-bound complexes between synaptotagmin-1 and the
neuronal SNARE complex, one of which was determined with diffraction data from
an X-ray free-electron laser, leading to an atomic-resolution structure with
accurate rotamer assignments for many side chains. The structures reveal several
interfaces, including a large, specific, Ca(2+)-independent and conserved
interface. Tests of this interface by mutagenesis suggest that it is essential
for Ca(2+)-triggered neurotransmitter release in mouse hippocampal neuronal
synapses and for Ca(2+)-triggered vesicle fusion in a reconstituted system. We
propose that this interface forms before Ca(2+) triggering, moves en bloc as
Ca(2+) influx promotes the interactions between synaptotagmin-1 and the plasma
membrane, and consequently remodels the membrane to promote fusion, possibly in
conjunction with other interfaces.
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