Proteopedia

3mw2

Crystal structure of beta-neurexin 1 with the splice insert 4Crystal structure of beta-neurexin 1 with the splice insert 4

Structural highlights

3mw2 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.69Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NRX1A_MOUSE Cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N-terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)-triggered exocytosis of secretory granules in pituitary gland. They may effect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latrotoxin from spider venom.[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

Alternatively spliced beta-neurexins (beta-NRXs) and neuroligins (NLs) are thought to have distinct extracellular binding affinities, potentially providing a beta-NRX/NL synaptic recognition code. We utilized surface plasmon resonance to measure binding affinities between all combinations of alternatively spliced beta-NRX 1-3 and NL 1-3 ectodomains. Binding was observed for all beta-NRX/NL pairs. The presence of the NL1 B splice insertion lowers beta-NRX binding affinity by approximately 2-fold, while beta-NRX splice insertion 4 has small effects that do not synergize with NL splicing. New structures of glycosylated beta-NRXs 1 and 2 containing splice insertion 4 reveal that the insertion forms a new beta strand that replaces the beta10 strand, leaving the NL binding site intact. This helps to explain the limited effect of splice insert 4 on NRX/NL binding affinities. These results provide new structural insights and quantitative binding information to help determine whether and how splice isoform choice plays a role in beta-NRX/NL-mediated synaptic recognition.

Splice form dependence of beta-neurexin/neuroligin binding interactions.,Koehnke J, Katsamba PS, Ahlsen G, Bahna F, Vendome J, Honig B, Shapiro L, Jin X Neuron. 2010 Jul 15;67(1):61-74. PMID:20624592[7]

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

See Also

References

  1. ↑ Geppert M, Khvotchev M, Krasnoperov V, Goda Y, Missler M, Hammer RE, Ichtchenko K, Petrenko AG, Sudhof TC. Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action. J Biol Chem. 1998 Jan 16;273(3):1705-10. PMID:9430716
  2. ↑ Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer RE, Gottmann K, Sudhof TC. Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature. 2003 Jun 26;423(6943):939-48. PMID:12827191 doi:http://dx.doi.org/10.1038/nature01755
  3. ↑ Kattenstroth G, Tantalaki E, Sudhof TC, Gottmann K, Missler M. Postsynaptic N-methyl-D-aspartate receptor function requires alpha-neurexins. Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2607-12. PMID:14983056
  4. ↑ Dudanova I, Sedej S, Ahmad M, Masius H, Sargsyan V, Zhang W, Riedel D, Angenstein F, Schild D, Rupnik M, Missler M. Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of secretory granules. J Neurosci. 2006 Oct 11;26(41):10599-613. PMID:17035546 doi:http://dx.doi.org/10.1523/JNEUROSCI.1913-06.2006
  5. ↑ Sons MS, Busche N, Strenzke N, Moser T, Ernsberger U, Mooren FC, Zhang W, Ahmad M, Steffens H, Schomburg ED, Plomp JJ, Missler M. alpha-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction. Neuroscience. 2006;138(2):433-46. Epub 2006 Jan 10. PMID:16406382 doi:http://dx.doi.org/10.1016/j.neuroscience.2005.11.040
  6. ↑ Matsuda K, Yuzaki M. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci. 2011 Apr;33(8):1447-61. doi: 10.1111/j.1460-9568.2011.07638.x., Epub 2011 Mar 17. PMID:21410790 doi:http://dx.doi.org/10.1111/j.1460-9568.2011.07638.x
  7. ↑ Koehnke J, Katsamba PS, Ahlsen G, Bahna F, Vendome J, Honig B, Shapiro L, Jin X. Splice form dependence of beta-neurexin/neuroligin binding interactions. Neuron. 2010 Jul 15;67(1):61-74. PMID:20624592 doi:10.1016/j.neuron.2010.06.001

3mw2, resolution 2.69Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3mw2&oldid=4210073"