3ASI

Alpha-Neurexin-1 ectodomain fragment; LNS5-EGF3-LNS6

Summary for 3ASI

• Entry DOI: 10.2210/pdb3asi/pdb
• Descriptor: Neurexin-1-alpha, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: beta-sandwich, cell adhesion, synapse maturation, neuroligin, n-glycosylation, membrane
• Biological source: Bos taurus (bovine)
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): Q28146
• Total number of polymer chains: 1
• Total formula weight: 45099.60

Authors

Tanaka, H.,Nogi, T.,Yasui, N.,Takagi, J. (deposition date: 2010-12-13, release date: 2011-04-13, Last modification date: 2024-11-20)

Primary citation

Tanaka, H.,Nogi, T.,Yasui, N.,Iwasaki, K.,Takagi, J.
Structural Basis for Variant-Specific Neuroligin-Binding by alpha-Neurexin
Plos One, 6:e19411-e19411, 2011

PubMed Abstract: Neurexins (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. α-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 β-Nrx has but a single LNS domain. It has long been known that the larger α-Nrx and the shorter β-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 Nrx1α ectodomain, consisting of LNS5-EGF3-LNS6. The 2.3 Å-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 α-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 α-Nrx. This, combined with a low-resolution molecular envelope obtained by a single particle reconstruction performed on negatively stained full-length Nrx1α sample, allowed us to derive a structural model of the α-Nrx ectodomain. This model will help us understand not only how the large α-Nrx ectodomain is accommodated in the synaptic cleft, but also how the trans-synaptic adhesion mediated by α- and β-Nrxs could differentially affect synaptic structure and function.

PubMed: 21552542
DOI: 10.1371/journal.pone.0019411

Experimental method

X-RAY DIFFRACTION (2.3 Å)