An accurate model of polyglutamine

作者：Digambaranath Jyothi L; Campbell Tyler V; Chung Alfred; McPhail Michael J; Stevenson Karis E; Zohdy Mohamed A; Finke John M^*

来源：Proteins: Structure, Function, and Genetics , 2011, 79(5): 1427-1440.

DOI：10.1002/prot.22970

• time-resolved fluorescence
• resonance energy transfer
• circular dichroism
• triplet-state quenching
• molecular dynamics
• amyloid
• protein folding
• aggregation
• Huntington's disease

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(alpha)C(beta) 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(alpha)C(beta) models with random coil and extended beta-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) similar to 10-16 and is as compact as many folded proteins at Q(N) > 16. Proteins 2011; 79: 1427-1440.

• 出版日期2011-5