3r05

Structure of neurexin 1 alpha (domains LNS1-LNS6), with splice insert SS3

spinqualitylabelsall models 3r05, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3r05 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. Ligands: NAG 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 essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The alpha-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how alpha-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1alpha extracellular domain (n1alpha) to 2.65 A. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 A structure of n1alpha carrying splice insert SS#3 in LNS4 reveals that SS#3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables alpha-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function. The structure of neurexin 1alpha reveals features promoting a role as synaptic organizer.,Chen F, Venugopal V, Murray B, Rudenko G Structure. 2011 Jun 8;19(6):779-89. Epub 2011 May 27. PMID:21620716 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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