3asi | pdb_00003asi
Alpha-Neurexin-1 ectodomain fragment; LNS5-EGF3-LNS6
Structural highlights
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 PubMedNeurexins (Nrxs) are presynaptic membrane proteins with a single membrane-spanning domain that mediate asymmetric trans-synaptic cell adhesion by binding to their postsynaptic receptor neuroligins. alpha-Nrx has a large extracellular region comprised of multiple copies of laminin, neurexin, sex-hormone-binding globulin (LNS) domains and epidermal growth factor (EGF) modules, while that of beta-Nrx has but a single LNS domain. It has long been known that the larger alpha-Nrx and the shorter beta-Nrx show distinct binding behaviors toward different isoforms/variants of neuroligins, although the underlying mechanism has yet to be elucidated. Here, we describe the crystal structure of a fragment corresponding to the C-terminal one-third of the Nrx1alpha ectodomain, consisting of LNS5-EGF3-LNS6. The 2.3 A-resolution structure revealed the presence of a domain configuration that was rigidified by inter-domain contacts, as opposed to the more common flexible "beads-on-a-string" arrangement. Although the neuroligin-binding site on the LNS6 domain was completely exposed, the location of the alpha-Nrx specific LNS5-EGF3 segment proved incompatible with the loop segment inserted in the B+ neuroligin variant, which explains the variant-specific neuroligin recognition capability observed in alpha-Nrx. This, combined with a low-resolution molecular envelope obtained by a single particle reconstruction performed on negatively stained full-length Nrx1alpha sample, allowed us to derive a structural model of the alpha-Nrx ectodomain. This model will help us understand not only how the large alpha-Nrx ectodomain is accommodated in the synaptic cleft, but also how the trans-synaptic adhesion mediated by alpha- and beta-Nrxs could differentially affect synaptic structure and function. Structural Basis for Variant-Specific Neuroligin-Binding by alpha-Neurexin.,Tanaka H, Nogi T, Yasui N, Iwasaki K, Takagi J PLoS One. 2011 Apr 28;6(4):e19411. PMID:21552542[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
