Characterization of the solution structure of a neuroligin/beta-neurexin complex

Comoletti, Davide, Grishaev, Alexander, Whitten, Andrew E., Taylor, Palmer and Trewhella, Jill (2008). Characterization of the solution structure of a neuroligin/beta-neurexin complex. In: Karl Tsim and Bhupendra Doctor, Chemico-Biological Interactions. Proceedings of: The IX International Meeting on Cholinesterases. The IX International Meeting on Cholinesterases, Suzhou, China, (150-155). 6-10 May 2007. doi:10.1016/j.cbi.2008.04.040


Author Comoletti, Davide
Grishaev, Alexander
Whitten, Andrew E.
Taylor, Palmer
Trewhella, Jill
Title of paper Characterization of the solution structure of a neuroligin/beta-neurexin complex
Formatted title
Characterization of the solution structure of a neuroligin/β-neurexin complex
Conference name The IX International Meeting on Cholinesterases
Conference location Suzhou, China
Conference dates 6-10 May 2007
Proceedings title Chemico-Biological Interactions. Proceedings of: The IX International Meeting on Cholinesterases   Check publisher's open access policy
Journal name Chemico-Biological Interactions   Check publisher's open access policy
Place of Publication Amsterdam, Netherlands
Publisher Elsevier Ireland
Publication Year 2008
Sub-type Fully published paper
DOI 10.1016/j.cbi.2008.04.040
ISSN 0009-2797
1872-7786
Editor Karl Tsim
Bhupendra Doctor
Volume 175
Issue 1-3
Start page 150
End page 155
Total pages 6
Language eng
Formatted Abstract/Summary
Neuroligins are post-synaptic cell adhesion molecules that promote synaptic maturation and stabilization upon binding with pre-synaptic partners, the α- and β-neurexins. Using a combination of analytical ultracentrifugation, small angle X-ray, and neutron scattering, we have characterized the low-resolution three-dimensional structure of the extracellular domain of the neuroligins, free in solution, and in complex with β-neurexin. The globular extracellular domain of the neuroligins forms stable homodimers through a four-helix bundle typical of the cholinesterases and other members of the α/β-hydrolase fold family. The presence of the stalk region adds to the extracellular domain of neuroligin-1 an elongated structure, suggesting a rod-like nature of the stalk domain. Sedimentation equilibrium coupled with solution scattering data of the β-neurexin/neuroligin-1 complex indicated a 2:2 stoichiometry where two β-neurexin molecules bind to a neuroligin-1 dimer. Deuteration of neurexin allowed us to collect neutron scattering data that, in combination with other biochemical techniques, provide a basis for optimizing the positioning of each component in a detailed computational model of the neuroligin/neurexin complex. As several mutations of both neurexin and neuroligin genes have been linked to autism spectrum disorders and mental retardation, these new structures provide an important framework for the study of altered structure and function of these synaptic proteins.
© 2008 Elsevier Ireland Ltd. All rights reserved.
Subjects 0601 Biochemistry and Cell Biology
Keyword Synaptic adhesion molecules
Neuroligin
Neurexin
SAXS
Q-Index Code E1
Q-Index Status Provisional Code
Additional Notes Published under "Session III: Structure / Function-relationship of cholinesterases and their homologs: Oral presentations"

 
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Created: Fri, 19 Feb 2010, 20:53:51 EST by Sue Green on behalf of Institute for Molecular Bioscience