Cystatin forms a Tetramer through Structural Rearrangement of Domain-swapped Dimers prior to Amyloidogenesis

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• 作者：Sanders ; Anna ; Jeremy Craven ; C. ; Higgins ; Lee D. ; Giannini ; Silva ; Conroy ; Matthew J. ; Hounslow ; Andrea M. ; et. al.
• 关键词：cystatin ; amyloid intermediate ; CAA ; domain-swapping ; dimer ; hCC ; human cystatin C ; cC ; chicken cystatin ; GdnHCl ; guanidine hydrochloride ; CR ; Congo red ; ANS ; 8-anilino-1-naphthalene sulfonate ; M ; monomer ; D ; dimer ; T ; tetramer ; SEC ; size-exclusion chroma
• 刊名：Journal of Molecular Biology
• 出版年：2004
• 出版时间：February 6, 2004
• 年：2004
• 卷：336
• 期：1
• 页码：165-178
• 全文大小：1.25 M

文摘

The cystatins were the first amyloidogenic proteins to be shown to oligomerize through a 3D domain swapping mechanism. Here we show that, under conditions leading to the formation of amyloid deposits, the domain-swapped dimer of chicken cystatin further oligomerizes to a tetramer, prior to fibrillization. The tetramer has a very similar circular dichroism and fluorescence signature to the folded monomer and dimer structures, but exhibits some loss of dispersion in the ¹H-NMR spectrum. 8-Anilino-1-naphthalene sulfonate fluorescence enhancement indicates an increase in the degree of disorder. While the dimerization reaction is bimolecular and most likely limited by the availability of a predominantly unfolded form of the monomer, the tetramerization reaction is first-order. The tetramer is formed slowly (t_1/2