An accurate model of polyglutamine

Jyothi L. Digambaranath, Tyler V. Campbell, Alfred Chung, Michael Jesse McPhail, Karis E. Stevenson, Mohamed A. Zohdy, John M. Finke

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Polyglutamine repeats in proteins are highly correlated with amyloid formation and neurological disease. To better understand the molecular basis of glutamine repeat diseases, structural analysis of polyglutamine peptides as soluble monomers, oligomers, and insoluble amyloid fibrils is necessary. In this study, fluorescence resonance energy transfer (FRET) experiments and molecular dynamics simulations using different theoretical models of polyglutamine were conducted. This study demonstrates that a previously proposed simple C αC β model of polyglutamine, denoted as FCO, accurately reproduced the present FRET results and the results of previously published FRET, triplet-state quenching, and fluorescence correlation studies. Other simple C αC β models with random coil and extended β-strand parameters, and all-atom models with parm96 and parm99SB force fields, did not match the FRET result well. The FCO is an intrinsically disordered model with a high-effective persistence length producing extended peptides at short lengths (Q N < 10). Because of an increasing number of attractive Q-Q interactions at longer lengths, the FCO model becomes increasingly more compact at lengths between Q N ∼ 10-16 and is as compact as many folded proteins at Q N > 16.

Original languageEnglish (US)
Pages (from-to)1427-1440
Number of pages14
JournalProteins: Structure, Function and Bioinformatics
Volume79
Issue number5
DOIs
StatePublished - May 1 2011

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Fluorescence Resonance Energy Transfer
Amyloid
Peptides
Molecular Dynamics Simulation
Glutamine
Theoretical Models
Oligomers
Structural analysis
Fluorescence
Molecular dynamics
Quenching
Monomers
polyglutamine
Atoms
Computer simulation
Proteins
Experiments

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Digambaranath, J. L., Campbell, T. V., Chung, A., McPhail, M. J., Stevenson, K. E., Zohdy, M. A., & Finke, J. M. (2011). An accurate model of polyglutamine. Proteins: Structure, Function and Bioinformatics, 79(5), 1427-1440. https://doi.org/10.1002/prot.22970
Digambaranath, Jyothi L. ; Campbell, Tyler V. ; Chung, Alfred ; McPhail, Michael Jesse ; Stevenson, Karis E. ; Zohdy, Mohamed A. ; Finke, John M. / An accurate model of polyglutamine. In: Proteins: Structure, Function and Bioinformatics. 2011 ; Vol. 79, No. 5. pp. 1427-1440.
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Digambaranath, JL, Campbell, TV, Chung, A, McPhail, MJ, Stevenson, KE, Zohdy, MA & Finke, JM 2011, 'An accurate model of polyglutamine', Proteins: Structure, Function and Bioinformatics, vol. 79, no. 5, pp. 1427-1440. https://doi.org/10.1002/prot.22970

An accurate model of polyglutamine. / Digambaranath, Jyothi L.; Campbell, Tyler V.; Chung, Alfred; McPhail, Michael Jesse; Stevenson, Karis E.; Zohdy, Mohamed A.; Finke, John M.

In: Proteins: Structure, Function and Bioinformatics, Vol. 79, No. 5, 01.05.2011, p. 1427-1440.

Research output: Contribution to journalArticle

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Digambaranath JL, Campbell TV, Chung A, McPhail MJ, Stevenson KE, Zohdy MA et al. An accurate model of polyglutamine. Proteins: Structure, Function and Bioinformatics. 2011 May 1;79(5):1427-1440. https://doi.org/10.1002/prot.22970