کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1987964 1540319 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Circular dichroism studies of extracellular domains of human nicotinic acetylcholine receptors provide an insight into their structure
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Circular dichroism studies of extracellular domains of human nicotinic acetylcholine receptors provide an insight into their structure
چکیده انگلیسی

The extracellular domains (ECDs) of human nicotinic acetylcholine receptors (nAChRs) are of major pharmacological interest as drug targets in the autoimmune disease myasthenia gravis and in various neurological disorders. We have previously expressed and purified the human muscle α1-, β1-, γ- and ɛ-nAChR-ECDs, as well as the wild type and a mutant of neuronal α7-ECD, in yeast Pichia pastoris. The far-UV circular dichroism (CD) studies of these ECDs, presented here, revealed a major prevalence of β-sheet (∼40%) and a small proportion of α-helical (∼5%) structure for all ECDs, in good agreement with the secondary structure composition of the Torpedo muscle-type nAChR-ECDs and in less, but considerable, agreement with that of the homologous invertebrate acetylcholine-binding proteins (AChBPs). The near-UV CD studies of these nAChR-ECDs indicated well-defined tertiary structures, as was previously suggested by biochemical and immunochemical studies. Furthermore, the binding of cholinergic ligands to the mutant of α7-ECD resulted in no changes in its secondary structure, but revealed significant local conformational changes. Our present studies probe the structure of human nAChR-ECDs for the first time and further suggest that our expressed proteins fold to a near-native conformation, thus being suitable for further structural studies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 41, Issue 4, 1 October 2007, Pages 423–429
نویسندگان
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