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Biophysical characterization of the unstructured cytoplasmic domain of the human neuronal adhesion protein neuroligin 3

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  • Aviv Paz, Weizmann Institute of Science, Israel
  • Tzviya Zeev-Ben-Mordehai, Weizmann Institute of Science, Unknown
  • Martin Lundqvist, University of Groningen, Unknown
  • Eilon Sherman, Department of Chemical Physics, Weizmann Institute of Science, Rehovot, Israel., Unknown
  • Efstratios Mylonas, European Molecular Biology Laboratory Hamburg, Unknown
  • K. Lev Weiner, Weizmann Institute of Science, Unknown
  • Gilad Haran, Department of Chemical Physics, Weizmann Institute of Science, Rehovot, Israel., Unknown
  • Dmitri I. Svergun, European Molecular Biology Laboratory Hamburg, Germany
  • F. A A Mulder
  • Joel L. Sussman, Weizmann Institute of Science, Israel
  • Israel Silman, Weizmann Institute of Science, Israel

Cholinesterase-like adhesion molecules (CLAMs) are a family of neuronal cell adhesion molecules with important roles in synaptogenesis, and in maintaining structural and functional integrity of the nervous system. Our earlier study on the cytoplasmic domain of one of these CLAMs, the Drosophila protein, gliotactin, showed that it is intrinsically unstructured in vitro. Bioinformatic analysis suggested that the cytoplasmic domains of other CLAMs are also intrinsically unstructured, even though they bear no sequence homology to each other or to any known protein. In this study, we overexpress and purify the cytoplasmic domain of human neuroligin 3, notwithstanding its high sensitivity to the Escherichia coli endogenous proteases that cause its rapid degradation. Using bioinformatic analysis, sensitivity to proteases, size exclusion chromatography, fluorescence correlation spectroscopy, analytical ultracentrifugation, small angle x-ray scattering, circular dichroism, electron spin resonance, and nuclear magnetic resonance, we show that the cytoplasmic domain of human neuroligin 3 is intrinsically unstructured. However, several of these techniques indicate that it is not fully extended, but becomes significantly more extended under denaturing conditions.

Original languageEnglish
JournalBiophysical Journal
Volume95
Issue4
Pages (from-to)1928-1944
Number of pages17
ISSN0006-3495
DOIs
Publication statusPublished - 15 Aug 2008
Externally publishedYes

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