期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 45, 页码 16764-16769出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0608175103
关键词
chain collapse; poor solvent
资金
- NIA NIH HHS [R01 AG 19322, R01 AG019322] Funding Source: Medline
- NIDDK NIH HHS [R01 DK013332, DK 13332] Funding Source: Medline
We have used fluorescence correlation spectroscopy measurements to quantify the hydrodynamic sizes of monomeric polyglutamine as a function of chain length (N) by measuring the scaling of translational diffusion times (T-D) for the peptide series (Gly)(Gln)(N)-Cys-LyS(2) in aqueous solution. We find that TD scales with N as ToNv and therefore In(T-D) = In(T-o) + vIn(N). The values for v and In(T-o) are 0.32 +/- 0.02 and 3.04 +/- 0.08, respectively. Based on these observations, we conclude that water is a polymeric poor solvent for polyglutamine. Previous studies have shown that monomeric polyglutamine is intrinsically disordered. These observations combined with our fluorescence correlation spectroscopy data suggest that the ensemble for monomeric polyglutamine is made up of a heterogeneous collection of collapsed structures. This result is striking because the preference for collapsed structures arises despite the absence of residues deemed to be hydrophobic in the sequence constructs studied. Working under the assumption that the driving forces for collapse are similar to those for aggregation, we discuss the implications of our results for the thermodynamics and kinetics of polyglutamine aggregation, a process that has been implicated in the molecular mechanism of Huntington's disease.
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