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* Residue conservation analysis
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PDB id:
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Cell adhesion/cell adhesion
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Title:
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Crystal structure of the neuroligin-1/neurexin-1beta synapti complex
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Structure:
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Neuroligin-1. Chain: a, b, c, d. Fragment: extracellular esterase domain of neuroligin-1. Synonym: neuroligin i. Engineered: yes. Neurexin-1-beta. Chain: e, f, g, h. Fragment: extracellular lns domain of neurexin-1beta. Synonym: neurexin i-beta.
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Source:
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Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: nlgn1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: nrxn1.
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Resolution:
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3.50Å
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R-factor:
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0.246
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R-free:
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0.276
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Authors:
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D.Arac,A.A.Boucard,E.Ozkan,P.Strop,E.Newell,T.C.Sudhof,A.T.B
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Key ref:
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D.Araç
et al.
(2007).
Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions.
Neuron,
56,
992-1003.
PubMed id:
DOI:
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Date:
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01-Dec-07
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Release date:
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18-Dec-07
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PROCHECK
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Headers
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References
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Gene Ontology (GO) functional annotation
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Cellular component
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membrane
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1 term
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Biological process
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cell adhesion
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1 term
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DOI no:
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Neuron
56:992-1003
(2007)
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PubMed id:
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Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions.
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D.Araç,
A.A.Boucard,
E.Ozkan,
P.Strop,
E.Newell,
T.C.Südhof,
A.T.Brunger.
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ABSTRACT
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Neurexins and neuroligins provide trans-synaptic connectivity by the
Ca2+-dependent interaction of their alternatively spliced extracellular domains.
Neuroligins specify synapses in an activity-dependent manner, presumably by
binding to neurexins. Here, we present the crystal structures of neuroligin-1 in
isolation and in complex with neurexin-1 beta. Neuroligin-1 forms a constitutive
dimer, and two neurexin-1 beta monomers bind to two identical surfaces on the
opposite faces of the neuroligin-1 dimer to form a heterotetramer. The
neuroligin-1/neurexin-1 beta complex exhibits a nanomolar affinity and includes
a large binding interface that contains bound Ca2+. Alternatively spliced sites
in neurexin-1 beta and in neuroligin-1 are positioned nearby the binding
interface, explaining how they regulate the interaction. Structure-based
mutations of neuroligin-1 at the interface disrupt binding to neurexin-1 beta,
but not the folding of neuroligin-1 and confirm the validity of the binding
interface of the neuroligin-1/neurexin-1 beta complex. Our results provide
molecular insights for understanding the role of cell-adhesion proteins in
synapse function.
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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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H.Zhao,
S.Xiao,
X.Kong,
J.Wang,
X.Cao,
W.Gencheng,
H.H.Loh,
and
P.Y.Law
(2011).
Neuron-glial cell communication in the traumatic stress-induced immunomodulation.
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Synapse, 65,
433-440.
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S.L.Shipman,
E.Schnell,
T.Hirai,
B.S.Chen,
K.W.Roche,
and
R.A.Nicoll
(2011).
Functional dependence of neuroligin on a new non-PDZ intracellular domain.
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Nat Neurosci, 14,
718-726.
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A.Thyagarajan,
and
A.Y.Ting
(2010).
Imaging activity-dependent regulation of neurexin-neuroligin interactions using trans-synaptic enzymatic biotinylation.
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Cell, 143,
456-469.
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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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P.G.Fuerst,
and
R.W.Burgess
(2009).
Adhesion molecules in establishing retinal circuitry.
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Curr Opin Neurobiol, 19,
389-394.
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S.H.Lim,
S.K.Kwon,
M.K.Lee,
J.Moon,
D.G.Jeong,
E.Park,
S.J.Kim,
B.C.Park,
S.C.Lee,
S.E.Ryu,
D.Y.Yu,
B.H.Chung,
E.Kim,
P.K.Myung,
and
J.R.Lee
(2009).
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
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EMBO J, 28,
3564-3578.
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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.K.Chadman,
S.Gong,
M.L.Scattoni,
S.E.Boltuck,
S.U.Gandhy,
N.Heintz,
and
J.N.Crawley
(2008).
Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice.
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Autism Res, 1,
147-158.
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K.Mossman,
and
A.Brunger
(2008).
Profile of Axel Brunger.
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Proc Natl Acad Sci U S A, 105,
10643-10645.
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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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T.C.Südhof
(2008).
Neuroligins and neurexins link synaptic function to cognitive disease.
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Nature, 455,
903-911.
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J.N.Levinson,
and
A.El-Husseini
(2007).
A crystal-clear interaction: relating neuroligin/neurexin complex structure to function at the synapse.
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Neuron, 56,
937-939.
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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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