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* Residue conservation analysis
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DOI no:
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Nat Struct Biol
15:50-56
(2008)
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PubMed id:
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Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.
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X.Chen,
H.Liu,
A.H.Shim,
P.J.Focia,
X.He.
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ABSTRACT
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The heterophilic synaptic adhesion molecules neuroligins and neurexins are
essential for establishing and maintaining neuronal circuits by modulating the
formation and maturation of synapses. The neuroligin-neurexin adhesion is
Ca2+-dependent and regulated by alternative splicing. We report a structure of
the complex at a resolution of 2.4 A between the mouse neuroligin-1 (NL1)
cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) LNS (laminin,
neurexin and sex hormone-binding globulin-like) domain. The structure revealed a
delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated
and solvent-supplemented interface, rendering it capable of being modulated by
alternative splicing and other regulatory factors. Thermodynamic data supported
a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at
the edge of the NL1-NX1beta interface. Mapping neuroligin mutations implicated
in autism indicated that most such mutations are structurally destabilizing,
supporting deficient neuroligin biosynthesis and processing as a common cause
for this brain disorder.
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Selected figure(s)
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Figure 1.
(a) His-tag pull-down assay showing effects of mutagenesis of
NX1  surface
residues on NL1 binding.
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Figure 5.
The mutated residues, NL1 Asp106 (corresponding to the NL4
G99S mutation), NL1 Lys414 (corresponding to the NL4 K378R
mutation), NL1 Arg473 (corresponding to the NL3 R451C mutation)
and NL1 Val439 (corresponding to the NL4 V403M mutation), are
colored green and shown in space-filling representation, and are
mapped on the NL1–NX1 complex
(ribbons). These residues are away from the binding and
dimerization interfaces, and are mostly buried.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2008,
15,
50-56)
copyright 2008.
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Figures were
selected
by an automated process.
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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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G.J.Wright,
and
P.Washbourne
(2011).
Neurexins, neuroligins and LRRTMs: synaptic adhesion getting fishy.
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J Neurochem,
117,
765-778.
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D.A.Jacques,
and
J.Trewhella
(2010).
Small-angle scattering for structural biology--expanding the frontier while avoiding the pitfalls.
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Protein Sci,
19,
642-657.
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D.Comoletti,
M.T.Miller,
C.M.Jeffries,
J.Wilson,
B.Demeler,
P.Taylor,
J.Trewhella,
and
T.Nakagawa
(2010).
The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition.
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Structure,
18,
1044-1053.
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P.Leone,
D.Comoletti,
G.Ferracci,
S.Conrod,
S.U.Garcia,
P.Taylor,
Y.Bourne,
and
P.Marchot
(2010).
Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions.
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EMBO J,
29,
2461-2471.
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PDB code:
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T.J.Siddiqui,
R.Pancaroglu,
Y.Kang,
A.Rooyakkers,
and
A.M.Craig
(2010).
LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development.
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J Neurosci,
30,
7495-7506.
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F.Carafoli,
N.J.Clout,
and
E.Hohenester
(2009).
Crystal structure of the LG1-3 region of the laminin alpha2 chain.
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J Biol Chem,
284,
22786-22792.
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PDB code:
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J.Ko,
C.Zhang,
D.Arac,
A.A.Boucard,
A.T.Brunger,
and
T.C.Südhof
(2009).
Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation.
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EMBO J,
28,
3244-3255.
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C.Reissner,
M.Klose,
R.Fairless,
and
M.Missler
(2008).
Mutational analysis of the neurexin/neuroligin complex reveals essential and regulatory components.
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Proc Natl Acad Sci U S A,
105,
15124-15129.
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K.C.Shen,
D.A.Kuczynska,
I.J.Wu,
B.H.Murray,
L.R.Sheckler,
and
G.Rudenko
(2008).
Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing.
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Structure,
16,
422-431.
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PDB codes:
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M.F.Bolliger,
J.Pei,
S.Maxeiner,
A.A.Boucard,
N.V.Grishin,
and
T.C.Südhof
(2008).
Unusually rapid evolution of Neuroligin-4 in mice.
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Proc Natl Acad Sci U S A,
105,
6421-6426.
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S.Biswas,
R.J.Russell,
C.J.Jackson,
M.Vidovic,
O.Ganeshina,
J.G.Oakeshott,
and
C.Claudianos
(2008).
Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera.
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PLoS ONE,
3,
e3542.
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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
