Length of polyglutamine tract affects secondary and tertiary structures of huntingtin protein.

Abstract

The role of polyglutamine (polyQ) tract on protein stability and disease pathology remains ambiguous. We monitored the unfolding/refolding patterns of huntingtin proteins with varying polyQ lengths. In the presence of urea, minor differences in unfolding and refolding efficiencies were observed. However, in the presence of guanidinium hydrochloride, the protein with a longer polyQ stretch was able to regain its secondary but not tertiary structure on step-wise removal of denaturant. Thus, in case of Huntington's disease, the higher aggregation propensity of the mutant protein is likely to be due to the lower stability of the protein due to elongated polyQ tract.

• Authors: Shivang N Vachharajani, Rajeev Kumar Chaudhary, Shivcharan Prasad, Ipsita Roy
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 51 Issue 5 Pg. 920-5 (Dec 2012) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 22835760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Nerve Tissue Proteins
• Peptide Fragments
• Peptides
• polyglutamine
• Urea
• Guanidine

Topics

• Guanidine (pharmacology)
• Nerve Tissue Proteins (chemistry)
• Peptide Fragments (chemistry)
• Peptides (chemistry)
• Protein Denaturation (drug effects)
• Protein Refolding (drug effects)
• Protein Stability (drug effects)
• Protein Structure, Secondary (drug effects)
• Protein Structure, Tertiary (drug effects)
• Urea (pharmacology)