Synaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleSynaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering.
Publication TypeJournal Article
Year of Publication2007
AuthorsComoletti, D, Grishaev, A, Whitten, AE, Tsigelny, I, Taylor, P, Trewhella, J
JournalStructure
Volume15
Issue6
Pagination693-705
Date Published2007 Jun
ISSN0969-2126
KeywordsAmino Acid Sequence, Animals, Cell Adhesion Molecules, Neuronal, Dimerization, Membrane Proteins, Models, Chemical, Models, Molecular, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neutron Diffraction, Protein Isoforms, Protein Structure, Secondary, Protein Structure, Tertiary, Recombinant Proteins, Scattering, Small Angle, Solubility, Synapses, X-Ray Diffraction
Abstract

Neuroligins are postsynaptic cell-adhesion proteins that associate with their presynaptic partners, the neurexins. Using small-angle X-ray scattering, we determined the shapes of the extracellular region of several neuroligin isoforms in solution. We conclude that the neuroligins dimerize via the characteristic four-helix bundle observed in cholinesterases, and that the connecting sequence between the globular lobes of the dimer and the cell membrane is elongated, projecting away from the dimer interface. X-ray scattering and neutron contrast variation data show that two neurexin monomers, separated by 107 A, bind at symmetric locations on opposite sides of the long axis of the neuroligin dimer. Using these data, we developed structural models that delineate the spatial arrangements of different neuroligin domains and their partnering molecules. As mutations of neurexin and neuroligin genes appear to be linked to autism, these models provide a structural framework for understanding altered recognition by these proteins in neurodevelopmental disorders.

DOI10.1016/j.str.2007.04.010
Alternate JournalStructure
PubMed ID17562316
PubMed Central IDPMC2677967
Grant ListP42 ES 10337 / ES / NIEHS NIH HHS / United States
P42 ES010337 / ES / NIEHS NIH HHS / United States
P42 ES010337-01 / ES / NIEHS NIH HHS / United States
R37 GM 18360 / GM / NIGMS NIH HHS / United States
R37 GM018360 / GM / NIGMS NIH HHS / United States
R37 GM018360-28 / GM / NIGMS NIH HHS / United States
/ / Intramural NIH HHS / United States