Fibrillogenic and non-fibrillogenic ensembles of SDS-bound human α-synuclein

Ahmad, Md. Faiz ; Ramakrishna, Tangirala ; Raman, Bakthisaran ; Mohan Rao, Ch. (2006) Fibrillogenic and non-fibrillogenic ensembles of SDS-bound human α-synuclein Journal of Molecular Biology, 364 (5). pp. 1061-1072. ISSN 0022-2836

Full text not available from this repository.

Official URL:

Related URL:


Fibril formation of α-synuclein is associated with several neurodegenerative diseases, including Parkinson's disease in humans. The anionic detergent sodium dodecyl sulfate (SDS) can accelerate the fibril formation in vitro. However, the molecular basis of this acceleration is not clear. Our study shows that native α-synuclein exhibits relatively less fibril growth despite providing fibril seeds for nucleation. The presence of SDS promotes the seeded fibril growth in a concentration-dependent manner, with an optimal concentration of 0.5–0.75 mM. We used isothermal calorimetry, hydrophobic dye binding and circular dichroism spectroscopy to characterize the protein–detergent interactions as a function of the concentration of SDS. Interaction of SDS with α-synuclein when studied by isothermal titration calorimetry and hydrophobic dye-binding reveals a similar characteristic optimal behavior between 0.5 mM and 0.75 mM SDS. The study shows two types of ensembles of α-synuclein and SDS: the fibrillogenic ensembles formed with optimal concentration of SDS around 0.5–0.75 mM are characterized by enhanced accessible hydrophobic surfaces and extended to partially helical conformation, while the less or non-fibrillogenic ensembles formed above 2 mM SDS are characterized by less accessible hydrophobic surfaces and maximal helical content. Little or no fibrillogenicity of the ensembles observed above 2 mM SDS could be partly because of the observed intrinsic instability of the fibrils under the condition.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:α-Synuclein; SDS; Parkinson's Disease; Amyloid; Isothermal Titration Calorimetry
ID Code:36867
Deposited On:16 Apr 2011 14:26
Last Modified:29 Nov 2011 10:08

Repository Staff Only: item control page