کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2189192 1096202 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The HC Fragment of Tetanus Toxin forms Stable, Concentration-dependent Dimers via an Intermolecular Disulphide Bond
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The HC Fragment of Tetanus Toxin forms Stable, Concentration-dependent Dimers via an Intermolecular Disulphide Bond
چکیده انگلیسی

Protein oligomerisation is a prerequisite for the toxicity of a number of bacterial toxins. Examples include the pore-forming cytotoxin streptolysin O, which oligomerises to form large pores in the membrane and the protective antigen of anthrax toxin, where a heptameric complex is essential for the delivery of lethal factor and edema factor to the cell cytosol. Binding of the clostridial neurotoxins to receptors on neuronal cells is well characterised, but little is known regarding the quaternary structure of these toxins and the role of oligomerisation in the intoxication process. We have investigated the oligomerisation of the receptor binding domain (HC) of tetanus toxin, which retains the binding and trafficking properties of the full-length toxin. Electrophoresis, size exclusion chromatography and mass spectrometry were used to demonstrate that HC undergoes concentration-dependent oligomerisation in solution. Reducing agents were found to affect HC oligomerisation and, using mutagenesis, Cys869 was shown to be essential for this process. Furthermore, the oligomeric state and quaternary structure of HC in solution was assessed using synchrotron small-angle X-ray scattering. Ab initio shape analysis and rigid body modelling coupled with mutagenesis data allowed the construction of an unequivocal model of dimeric HC in solution. We propose a possible mechanism for HC oligomerisation and discuss how this may relate to toxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 365, Issue 1, 5 January 2007, Pages 123–134
نویسندگان
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