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PDBsum entry 3kwt
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Metal binding protein
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PDB id
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3kwt
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References listed in PDB file
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Key reference
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Title
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Munc13 c2b domain is an activity-Dependent ca2+ regulator of synaptic exocytosis.
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Authors
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O.H.Shin,
J.Lu,
J.S.Rhee,
D.R.Tomchick,
Z.P.Pang,
S.M.Wojcik,
M.Camacho-Perez,
N.Brose,
M.Machius,
J.Rizo,
C.Rosenmund,
T.C.Südhof.
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Ref.
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Nat Struct Biol, 2010,
17,
280-288.
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PubMed id
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Abstract
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Munc13 is a multidomain protein present in presynaptic active zones that
mediates the priming and plasticity of synaptic vesicle exocytosis, but the
mechanisms involved remain unclear. Here we use biophysical, biochemical and
electrophysiological approaches to show that the central C(2)B domain of Munc13
functions as a Ca(2+) regulator of short-term synaptic plasticity. The crystal
structure of the C(2)B domain revealed an unusual Ca(2+)-binding site with an
amphipathic alpha-helix. This configuration confers onto the C(2)B domain unique
Ca(2+)-dependent phospholipid-binding properties that favor
phosphatidylinositolphosphates. A mutation that inactivated Ca(2+)-dependent
phospholipid binding to the C(2)B domain did not alter neurotransmitter release
evoked by isolated action potentials, but it did depress release evoked by
action-potential trains. In contrast, a mutation that increased Ca(2+)-dependent
phosphatidylinositolbisphosphate binding to the C(2)B domain enhanced release
evoked by isolated action potentials and by action-potential trains. Our data
suggest that, during repeated action potentials, Ca(2+) and
phosphatidylinositolphosphate binding to the Munc13 C(2)B domain potentiate
synaptic vesicle exocytosis, thereby offsetting synaptic depression induced by
vesicle depletion.
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Secondary reference #1
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Title
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Calmodulin and munc13 form a ca2+ sensor/effector complex that controls short-Term synaptic plasticity.
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Authors
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H.J.Junge,
J.S.Rhee,
O.Jahn,
F.Varoqueaux,
J.Speiss,
M.N.Waxham,
C.Rosenmund,
N.Brose.
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Ref.
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cell(cambridge,mass ), 2004,
118,
389.
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Secondary reference #2
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Title
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Munc-13 is essential for fusion competence of glutamatergic synaptic vesicles.
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Authors
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I.Augustin,
C.Rosenmund,
T.C.Sudhof,
N.Brose.
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Ref.
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nature, 1999,
400,
457.
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Secondary reference #3
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Title
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Mammalian homologues of c. Elegans unc-13 gene define novel family of c2-Domain proteins.
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Authors
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N.Brose,
K.Hofmann,
Y.Hata,
T.C.Sudhof.
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Ref.
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j biol chem, 1995,
270,
25273.
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