UV Resonance Raman Structural Characterization of an (In)soluble Polyglutamine Peptide

Overview

Journal J Phys Chem B

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Feb 6

PMID 30717595

Citations 3

Authors

Ryan S Jakubek

Stephen E White

Sanford A Asher

Affiliations

Soon will be listed here.

Abstract

Fibrillization of polyglutamine (polyQ) tracts in proteins is implicated in at least 10 neurodegenerative diseases. This generates great interest in the structure and the aggregation mechanism(s) of polyQ peptides. The fibrillization of polyQ is thought to result from the peptide's insolubility in aqueous solutions; longer polyQ tracts show decreased aqueous solution solubility, which is thought to lead to faster fibrillization kinetics. However, few studies have characterized the structure(s) of polyQ peptides with low solubility. In the work here, we use UV resonance Raman spectroscopy to examine the secondary structures, backbone hydrogen bonding, and side chain hydrogen bonding for a variety of solution-state, solid, and fibril forms of DQK (Q20). Q20 is insoluble in water and has a β-strand-like conformation with extensive inter- and intrapeptide hydrogen bonding in both dry and aqueous environments. We find that Q20 has weaker backbone-backbone and backbone-side chain hydrogen bonding and is less ordered compared to that of polyQ fibrils. Interestingly, we find that the insoluble Q20 will form fibrils when incubated in water at room temperature for ∼5 h. Also, Q20 can be prepared using a well-known disaggregation procedure to produce a water-soluble PPII-like conformation with negligible inter- and intrapeptide hydrogen bonding and a resistance to aggregation.

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pH-controlled stacking direction of the β-strands in peptide fibrils.

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Polyglutamine Solution-State Structural Propensity Is Repeat Length Dependent.

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