3b3q | pdb_00003b3q

Crystal structure of a synaptic adhesion complex

Structural highlights

3b3q is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	CA, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NLGN1_MOUSE Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep (PubMed:23716671). The protein is involved in nervous system development.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.,Chen X, Liu H, Shim AH, Focia PJ, He X Nat Struct Mol Biol. 2008 Jan;15(1):50-6. Epub 2007 Dec 16. PMID:18084303^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Scheiffele P, Fan J, Choih J, Fetter R, Serafini T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell. 2000 Jun 9;101(6):657-69. PMID:10892652
↑ Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell. 2004 Dec 29;119(7):1013-26. PMID:15620359 doi:10.1016/j.cell.2004.11.035
↑ Varoqueaux F, Aramuni G, Rawson RL, Mohrmann R, Missler M, Gottmann K, Zhang W, Sudhof TC, Brose N. Neuroligins determine synapse maturation and function. Neuron. 2006 Sep 21;51(6):741-54. PMID:16982420 doi:https://dx.doi.org/10.1016/j.neuron.2006.09.003
↑ El Helou J, Bélanger-Nelson E, Freyburger M, Dorsaz S, Curie T, La Spada F, Gaudreault PO, Beaumont É, Pouliot P, Lesage F, Frank MG, Franken P, Mongrain V. Neuroligin-1 links neuronal activity to sleep-wake regulation. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9974-9. PMID:23716671 doi:10.1073/pnas.1221381110
↑ Nakanishi M, Nomura J, Ji X, Tamada K, Arai T, Takahashi E, Bućan M, Takumi T. Functional significance of rare neuroligin 1 variants found in autism. PLoS Genet. 2017 Aug 25;13(8):e1006940. PMID:28841651 doi:10.1371/journal.pgen.1006940
↑ Zhang P, Lu H, Peixoto RT, Pines MK, Ge Y, Oku S, Siddiqui TJ, Xie Y, Wu W, Archer-Hartmann S, Yoshida K, Tanaka KF, Aricescu AR, Azadi P, Gordon MD, Sabatini BL, Wong ROL, Craig AM. Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships. Cell. 2018 Sep 6;174(6):1450-1464.e23. PMID:30100184 doi:10.1016/j.cell.2018.07.002
↑ Chen X, Liu H, Shim AH, Focia PJ, He X. Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions. Nat Struct Mol Biol. 2008 Jan;15(1):50-6. Epub 2007 Dec 16. PMID:18084303 doi:10.1038/nsmb1350

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OCA

[1] Scheiffele P, Fan J, Choih J, Fetter R, Serafini T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell. 2000 Jun 9;101(6):657-69. PMID:10892652

[2] Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell. 2004 Dec 29;119(7):1013-26. PMID:15620359 doi:10.1016/j.cell.2004.11.035

[3] Varoqueaux F, Aramuni G, Rawson RL, Mohrmann R, Missler M, Gottmann K, Zhang W, Sudhof TC, Brose N. Neuroligins determine synapse maturation and function. Neuron. 2006 Sep 21;51(6):741-54. PMID:16982420 doi:https://dx.doi.org/10.1016/j.neuron.2006.09.003

[4] El Helou J, Bélanger-Nelson E, Freyburger M, Dorsaz S, Curie T, La Spada F, Gaudreault PO, Beaumont É, Pouliot P, Lesage F, Frank MG, Franken P, Mongrain V. Neuroligin-1 links neuronal activity to sleep-wake regulation. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9974-9. PMID:23716671 doi:10.1073/pnas.1221381110

[5] Nakanishi M, Nomura J, Ji X, Tamada K, Arai T, Takahashi E, Bućan M, Takumi T. Functional significance of rare neuroligin 1 variants found in autism. PLoS Genet. 2017 Aug 25;13(8):e1006940. PMID:28841651 doi:10.1371/journal.pgen.1006940

[6] Zhang P, Lu H, Peixoto RT, Pines MK, Ge Y, Oku S, Siddiqui TJ, Xie Y, Wu W, Archer-Hartmann S, Yoshida K, Tanaka KF, Aricescu AR, Azadi P, Gordon MD, Sabatini BL, Wong ROL, Craig AM. Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships. Cell. 2018 Sep 6;174(6):1450-1464.e23. PMID:30100184 doi:10.1016/j.cell.2018.07.002

[7] Chen X, Liu H, Shim AH, Focia PJ, He X. Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions. Nat Struct Mol Biol. 2008 Jan;15(1):50-6. Epub 2007 Dec 16. PMID:18084303 doi:10.1038/nsmb1350

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3b3q | pdb_00003b3q

Crystal structure of a synaptic adhesion complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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Proteopedia Page Contributors and Editors (what is this?)

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