Crystal structures of β-neurexin 1 and β-neurexin 2 ectodomains and dynamics of splice insertion sequence 4

Koehnke, J. , Jin, X., Trbovic, N., Katsamba, P. S., Brasch, J., Ahlsen, G., Scheiffele, P., Honig, B., Palmer, A. G. and Shapiro, L. (2008) Crystal structures of β-neurexin 1 and β-neurexin 2 ectodomains and dynamics of splice insertion sequence 4. Structure, 16(3), pp. 410-421. (doi: 10.1016/j.str.2007.12.024) (PMID:18334216) (PMCID:PMC2750865)

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Abstract

Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca2+-dependent complexes that bridge neural synapses. β-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Δ. We present crystal structures of the Δ isoforms of the LNS domains from β-NRX1 and β-NRX2, crystallized in the presence of Ca2+ ions. The Ca2+-binding site is disordered in the β-NRX2 structure, but the 1.7 Å β-NRX1 structure reveals a single Ca2+ ion, ∼12 Å from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent β-NRX1 molecule. NMR studies of β-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that β-NRX insertion sequence 4 may function in roles independent of neuroligin binding.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Koehnke, Professor Jesko
Authors: Koehnke, J., Jin, X., Trbovic, N., Katsamba, P. S., Brasch, J., Ahlsen, G., Scheiffele, P., Honig, B., Palmer, A. G., and Shapiro, L.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Structure
Publisher:Elsevier
ISSN:0969-2126
ISSN (Online):1878-4186

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