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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-1-7
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pubmed:databankReference |
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pubmed:abstractText |
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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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-10520997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-10892652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-12669065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-14522992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-14963808,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15150161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15152050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15358863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15620359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15622415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15681343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-15797875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16242404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16337695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16337696,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16624946,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16648374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16772286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16794786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16846852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-16982420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17034946,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17042500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17158149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17322880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17562316,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17582332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17721508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-17823315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-2025413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-7736595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-8521480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-8576240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-9325340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-9757107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-9856994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-9925793,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18084303-9927700
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1545-9985
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
50-6
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pubmed:dateRevised |
2011-9-7
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pubmed:meshHeading |
pubmed-meshheading:18084303-Alternative Splicing,
pubmed-meshheading:18084303-Autistic Disorder,
pubmed-meshheading:18084303-Binding Sites,
pubmed-meshheading:18084303-Calcium,
pubmed-meshheading:18084303-Cell Adhesion,
pubmed-meshheading:18084303-Cell Adhesion Molecules,
pubmed-meshheading:18084303-Cell Adhesion Molecules, Neuronal,
pubmed-meshheading:18084303-Humans,
pubmed-meshheading:18084303-Membrane Proteins,
pubmed-meshheading:18084303-Models, Molecular,
pubmed-meshheading:18084303-Nerve Tissue Proteins,
pubmed-meshheading:18084303-Neural Cell Adhesion Molecules,
pubmed-meshheading:18084303-Protein Conformation,
pubmed-meshheading:18084303-Synapses
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pubmed:year |
2008
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pubmed:articleTitle |
Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.
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pubmed:affiliation |
Northwestern University Feinberg School of Medicine, Department of Molecular Pharmacology & Biological Chemistry, Searle 8-417, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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