6cw1

From Proteopedia

(Difference between revisions)

Revision as of 06:47, 24 October 2018

Crystal structure of Neurexin-1 alpha ectodomain fragment, L2-L3

Structural highlights

6cw1 is a 2 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NRXN1 (BOVIN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NRX1A_BOVIN] 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 (By similarity). 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.

Publication Abstract from PubMed

alpha-Neurexins are synaptic organizing molecules implicated in neuropsychiatric disorders. They bind and arrange an array of different partners in the synaptic cleft. The extracellular region of neurexin 1alpha (n1alpha) contains six LNS domains (L1-L6) interspersed by three Egf-like repeats. N1alpha must encode highly evolved structure-function relationships in order to fit into the narrow confines of the synaptic cleft, and also recruit its large, membrane-bound partners. Internal molecular flexibility could provide a solution, however, it is challenging to delineate because currently no structural methods permit high resolution structure determination of large, flexible, multi-domain protein molecules. To investigate the structural plasticity of n1alpha, in particular the conformation of domains that carry validated binding sites for different protein partners, we used a panel of structural techniques. Individual particle electron tomography (IPET) revealed that the N-terminally and C-terminally tethered domains, L1 and L6, have a surprisingly limited range of conformational freedom with respect to the linear central core containing L2 through L5. A 2.8A crystal structure revealed an unexpected arrangement of the L2 and L3 domains. SAXS and ET indicated that incorporation of the alternative splice insert SS6 relieves the restricted conformational freedom between L5 and L6, suggesting that SS6 may work as a molecular toggle. The architecture of n1alpha thus encodes a combination of rigid and flexibly tethered domains that are uniquely poised to work together to promote its organizing function in the synaptic cleft, and may permit allosterically regulated and/or concerted protein partner binding.

Structural Plasticity of Neurexin 1alpha: Implications for its Role as Synaptic Organizer.,Liu J, Misra A, Reddy S, White MA, Ren G, Rudenko G J Mol Biol. 2018 Sep 4. pii: S0022-2836(18)30192-X. doi:, 10.1016/j.jmb.2018.08.026. PMID:30193986^[1]

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

References

↑ Liu J, Misra A, Reddy S, White MA, Ren G, Rudenko G. Structural Plasticity of Neurexin 1alpha: Implications for its Role as Synaptic Organizer. J Mol Biol. 2018 Sep 4. pii: S0022-2836(18)30192-X. doi:, 10.1016/j.jmb.2018.08.026. PMID:30193986 doi:http://dx.doi.org/10.1016/j.jmb.2018.08.026

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cw1"

@@ Line 3: / Line 3: @@
 <StructureSection load='6cw1' size='340' side='right' caption='[[6cw1]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cw1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CW1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cw1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CW1 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cw1 OCA], [http://pdbe.org/6cw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cw1 RCSB], [http://www.ebi.ac.uk/pdbsum/6cw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cw1 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NRXN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cw1 OCA], [http://pdbe.org/6cw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cw1 RCSB], [http://www.ebi.ac.uk/pdbsum/6cw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cw1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Bovin]]
 [[Category: Misra, A]]
 [[Category: Rudenko, G]]

6cw1

From Proteopedia

Revision as of 06:47, 24 October 2018

Crystal structure of Neurexin-1 alpha ectodomain fragment, L2-L3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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