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Small angle x‐ray scattering and analytical ultracentrifugation characterization of the extracellular domain of α‐neurexin, alone and in complex with neuroligin‐1
Author(s) -
Comoletti Davide,
Miller Meghan T,
Wilson Jennifer,
Trewhella Jill,
Taylor Palmer
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.823.19
Subject(s) - neurexin , neuroligin , small angle x ray scattering , chemistry , biophysics , crystallography , biochemistry , biology , scattering , physics , postsynaptic potential , optics , receptor
Presynaptic cell adhesion protein α‐neurexin associates with neuroligins, its postsynaptic partner. Polymorphisms of the coding regions of neurexin and neuroligin genes were recently found to be associated with autism spectrum disorders and mental retardation. By small angle x‐ray scattering (SAXS) and analytical ultracentrifugation we have determined the basic structural parameters (maximum dimension, radius of gyration, molecular mass and volume) of the extracellular domain of α‐neurexin. Using the same data, we are now working on the determination their low resolution structure. Gel filtration chromatography and SAXS data suggest that the extracellular domain of α‐neurexin is monomeric in solution. Preliminary binding data on the α‐neurexin/neuroligin‐1 complex suggest a 2:2 stoichiometry where two α‐neurexin molecules bind to a neuroligin‐1 dimer. As mutations of neurexin and neuroligin genes appear linked to autism, these new structural models provide a framework for understanding altered recognition by these proteins in neuro‐developmental disorders. This work was supported by: USPHS Grant R37 GM‐18360 and NIEHS to PT, NAAR #843 and CAN Pilot Research Award to DC; DOE/SC Grant and ARC Federation Fellowship to JT