Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/43098
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Type: | Journal article |
Title: | Site-directed mutations in the C-terminal extension of human aB-Crystalline affect chaperone function and block amyloid fibril formation |
Author: | Treweek, T. Ecroyd, H. Williams, D. Meehan, S. Carver, J. Walker, M. |
Citation: | PLoS One, 2007; 2(10):1-10 |
Publisher: | Public Library of Science |
Issue Date: | 2007 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Abraham, E. |
Abstract: | Background. Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including aB-crystallin, play a role in the prevention of protein deposition. Methodology/Principal Findings. A series of site-directed mutants of the human molecular chaperone, aBcrystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of aB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal extension of aB-crystallin resulted in proteins that had improved chaperone activity against amyloid fibril forming target proteins compared to the wild-type protein. Conclusions/Significance. Together, our results highlight the important role of the C-terminal region of aB-crystallin in regulating its secondary, tertiary and quaternary structure and conferring thermostability to the protein. The capacity to genetically modify aB-crystallin for improved ability to block amyloid fibril formation provides a platform for the future use of such engineered molecules in treatment of diseases caused by amyloid fibril formation. |
Keywords: | Humans Amyloid Glutamic Acid Lysine Proteins alpha-Crystallin B Chain Molecular Chaperones Codon Spectrometry, Mass, Electrospray Ionization Mutagenesis, Site-Directed Temperature Protein Structure, Quaternary Protein Structure, Secondary Protein Structure, Tertiary Mutation |
Description: | Copyright: 2007 Treweek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0001046 |
Grant ID: | ARC |
Published version: | http://dx.doi.org/10.1371/journal.pone.0001046 |
Appears in Collections: | Aurora harvest 6 Chemistry and Physics publications |
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