Polyglutamine repeats and beta-helix structure: molecular dynamics study

Proteins
Antonello MerlinoLuigi Vitagliano

Abstract

Neurodegenerative diseases are often associated with the formation of highly insoluble aggregates. Despite the efforts devoted to the characterization of these aggregates, their structure remains elusive. Several neurodegenerative diseases are characterized by the expansion of CAG repeats, which code for Gln. Among the structural models proposed for the aggregates observed in polyQ-linked diseases, the nanotube beta-helix model proposed by Perutz and colleagues Proc Natl Acad Sci U S A 2002;99:5591-5595 has been influential. In the present study, the stability of this beta-helix model has been investigated by performing molecular dynamics simulations on polyQ fragments of different lengths. The results indicate that models shorter than two full beta-helix turns are unstable and collapse toward irregular structures. On the other hand, longer beta-helix models, containing more than 40 residues, achieve a dynamic regular structure. This finding is in line with the observed threshold of Gln repeats (approximately 40) correlated with the insurgence of the disease. Notably, the structure of the final state of the models longer than 40 residues strictly depends on their size. A compact stable ellipsoidal structure is formed by the mod...Continue Reading

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Citations

May 27, 2010·Neuroscience Bulletin·Xiao-Hui HeZheng-Hong Qin
Mar 1, 2009·Interdisciplinary Sciences, Computational Life Sciences·Miki NakanoShigenori Tanaka
Mar 4, 2011·Interdisciplinary Sciences, Computational Life Sciences·Bryan M B VanschouwenStuart M Rothstein
Feb 8, 2011·Journal of Biomolecular Structure & Dynamics·Zheng-Li ZhouYih Ho
May 26, 2012·Biological Chemistry·Lilit AtanesyanWalter Schaffner
May 6, 2010·The Journal of Chemical Physics·Rozita Laghaei, Normand Mousseau
Mar 13, 2014·Journal of Molecular Cell Biology·Rachel L RedlerNikolay V Dokholyan
Jul 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Luciana EspositoLuigi Vitagliano
Oct 13, 2010·Molecular Phylogenetics and Evolution·Sonia VarrialeUmberto Oreste
Feb 5, 2008·Computational Biology and Chemistry·Hajime OgawaShigenori Tanaka
Feb 20, 2007·Journal of Molecular Biology·Luigi VitaglianoRita Berisio
Jul 10, 2012·The Journal of Physical Chemistry. B·Markus S MiettinenZoya Ignatova
Apr 16, 2009·The Journal of Physical Chemistry. B·Giulia RossettiPaolo Carloni
Dec 17, 2019·ACS Chemical Neuroscience·Sanda Nastasia Moldovean, Vasile Chiş

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