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Insights into the structure and function of the extracellular domain of alpha‐neurexin by single particle EM and surface plasmon resonance
Author(s) -
Miller Meghan Thorne,
Comoletti Davide,
Wilson Jennifer,
Nakagawa Teru,
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.823.18
Subject(s) - neurexin , neuroligin , surface plasmon resonance , chemistry , extracellular , biophysics , adhesion , biochemistry , microbiology and biotechnology , postsynaptic potential , biology , nanotechnology , materials science , receptor , organic chemistry , nanoparticle
Neurexins are a family of presynaptic cell‐adhesion membrane proteins that are important for synapse maintenance through contact with the postsynaptic neuroligin molecules. Several studies have indicated that mutations in these genes may play an important role in autism and mental retardation. Each neurexin gene contains two promoters corresponding to the α‐and β‐neurexins. While the extracellular domain of β ‐neurexin contains only a single LNS/LG domain, α ‐neurexin consists of six LNS/LG domains, including the β ‐neurexin domain, separated by three EGF domains. To investigate the conformation of the extracellular domain of α ‐neurexin we imaged purified protein using negative‐stain EM. Raw particle EM images suggest that the LNS/LG domains of α ‐neurexin exist in a mixture of different conformations. Additional experiments to obtain class averages and to investigate the effect of calcium and ligands on conformation are ongoing. Using surface plasmon resonance (SPR) we report a rank order of specificity for α ‐neurexin binding to the different neuroligins. Furthermore, we are using mutagenesis and SPR to help us understand the contribution of the different LNS/LG domains of α‐neurexin to neuroligin binding. This work was supported by: USPHS Grant R37 GM‐18360 and NIEHS to PT, and the Pharmacology Training Grant