Biophysical Characterization of the Unstructured Cytoplasmic Domain of the Human Neuronal Adhesion Protein Neuroligin 3

Sparad:
Bibliografiska uppgifter
I publikationen:Biophysical Journal vol. 95, no. 4 (Aug 15, 2008), p. 1928-1944
Huvudupphov: Paz, Aviv
Övriga upphov: Zeev-Ben-Mordehai, Tzviya, Lundqvist, Martin, Sherman, Eilon, Mylonas, Efstratios, Weiner, Lev, Haran, Gilad, Svergun, Dmitri I, Mulder, Frans A A, Sussman, Joel L, Silman, Israel
Utgiven:
Biophysical Society
Ämnen:
Länkar:Citation/Abstract
Full Text + Graphics
Full Text - PDF
Taggar: Lägg till en tagg
Inga taggar, Lägg till första taggen!

MARC

LEADER 00000nab a2200000uu 4500
001 215696058
003 UK-CbPIL
022 |a 0006-3495 
022 |a 1542-0086 
035 |a 215696058 
045 0 |b d20080815 
084 |a 18456828 
084 |a 36123  |2 nlm 
100 1 |a Paz, Aviv 
245 1 |a Biophysical Characterization of the Unstructured Cytoplasmic Domain of the Human Neuronal Adhesion Protein Neuroligin 3 
260 |b Biophysical Society  |c Aug 15, 2008 
513 |a Journal Article 
520 3 |a 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. [PUBLICATION ABSTRACT]   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. 
650 2 2 |a Biophysics  |x methods 
650 1 2 |a Cell Adhesion Molecules  |x chemistry 
650 2 2 |a Cell Adhesion Molecules, Neuronal 
650 2 2 |a Computer Simulation 
650 1 2 |a Cytoplasm  |x chemistry 
650 2 2 |a Humans 
650 1 2 |a Membrane Proteins  |x chemistry 
650 1 2 |a Membrane Proteins  |x ultrastructure 
650 1 2 |a Models, Chemical 
650 1 2 |a Models, Molecular 
650 1 2 |a Nerve Tissue Proteins  |x chemistry 
650 1 2 |a Nerve Tissue Proteins  |x ultrastructure 
650 2 2 |a Protein Conformation 
650 2 2 |a Protein Structure, Tertiary 
653 |a Proteins 
653 |a Molecules 
653 |a Mutation 
653 |a Nervous system 
653 |a Nuclear magnetic resonance--NMR 
653 |a E coli 
653 |a Cholinesterase 
653 |a Adhesion 
653 |a Environmental 
700 1 |a Zeev-Ben-Mordehai, Tzviya 
700 1 |a Lundqvist, Martin 
700 1 |a Sherman, Eilon 
700 1 |a Mylonas, Efstratios 
700 1 |a Weiner, Lev 
700 1 |a Haran, Gilad 
700 1 |a Svergun, Dmitri I 
700 1 |a Mulder, Frans A A 
700 1 |a Sussman, Joel L 
700 1 |a Silman, Israel 
773 0 |t Biophysical Journal  |g vol. 95, no. 4 (Aug 15, 2008), p. 1928-1944 
786 0 |d ProQuest  |t Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/215696058/abstract/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text + Graphics  |u https://www.proquest.com/docview/215696058/fulltextwithgraphics/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/215696058/fulltextPDF/embedded/6A8EOT78XXH2IG52?source=fedsrch