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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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Contents |
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* Residue conservation analysis
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Nat Struct Biol
17:280-288
(2010)
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PubMed id:
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Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.Fioravante,
and
W.G.Regehr
(2011).
Short-term forms of presynaptic plasticity.
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Curr Opin Neurobiol,
21,
269-274.
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L.Deng,
P.S.Kaeser,
W.Xu,
and
T.C.Südhof
(2011).
RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of Munc13.
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Neuron,
69,
317-331.
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R.Martín,
D.Bartolomé-Martín,
M.Torres,
and
J.Sánchez-Prieto
(2011).
Non-additive potentiation of glutamate release by phorbol esters and metabotropic mGlu7 receptor in cerebrocortical nerve terminals.
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J Neurochem,
116,
476-485.
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S.Schröder,
F.Fraternali,
X.Quan,
D.Scott,
F.Qian,
and
M.Pfuhl
(2011).
When a module is not a domain: the case of the REJ module and the redefinition of the architecture of polycystin-1.
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Biochem J,
435,
651-660.
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R.H.Law,
N.Lukoyanova,
I.Voskoboinik,
T.T.Caradoc-Davies,
K.Baran,
M.A.Dunstone,
M.E.D'Angelo,
E.V.Orlova,
F.Coulibaly,
S.Verschoor,
K.A.Browne,
A.Ciccone,
M.J.Kuiper,
P.I.Bird,
J.A.Trapani,
H.R.Saibil,
and
J.C.Whisstock
(2010).
The structural basis for membrane binding and pore formation by lymphocyte perforin.
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Nature,
468,
447-451.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
