Effects of the enlargement of polyglutamine segments on the structure and folding of ataxin-2 and ataxin-3 proteins.

J Biomol Struct Dyn 2017 Feb 20;35(3):504-519. Epub 2016 May 20.

a Department of Biomedical Informatics , University of Utah , Salt Lake City , UT , USA.

Spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) are two common autosomal-dominant inherited ataxia syndromes, both of which are related to the unstable expansion of trinucleotide CAG repeats in the coding region of the related ATXN2 and ATXN3 genes, respectively. The poly-glutamine (poly-Q) tract encoded by the CAG repeats has long been recognized as an important factor in disease pathogenesis and progress. In this study, using the I-TASSER method for 3D structure prediction, we investigated the effect of poly-Q tract enlargement on the structure and folding of ataxin-2 and ataxin-3 proteins. Our results show good agreement with the known experimental structures of the Josephin and UIM domains providing credence to the simulation results presented here, which show that the enlargement of the poly-Q region not only affects the local structure of these regions but also affects the structures of functional domains as well as the whole protein. The changes observed in the predicted models of the UIM domains in ataxin-3 when the poly-Q track is enlarged provide new insights on possible pathogenic mechanisms.

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http://dx.doi.org/10.1080/07391102.2016.1152199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580338PMC
February 2017
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