Site-directed mutations in the C-terminal extension of human αB-crystallin affect chaperone function and block amyloid fibril formation

Treweek, Teresa M., Ecroyd, Heath, Williams, Danielle M., Meehan, Sarah, Carver, John A. and Walker, Mark J. (2007) Site-directed mutations in the C-terminal extension of human αB-crystallin affect chaperone function and block amyloid fibril formation. PLoS One, 2 Article # e1046: . doi:10.1371/journal.pone.0001046


Author Treweek, Teresa M.
Ecroyd, Heath
Williams, Danielle M.
Meehan, Sarah
Carver, John A.
Walker, Mark J.
Title Site-directed mutations in the C-terminal extension of human αB-crystallin affect chaperone function and block amyloid fibril formation
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2007-10
Sub-type Article (original research)
DOI 10.1371/journal.pone.0001046
Open Access Status DOI
Volume 2
Issue Article # e1046
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Background: Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including αB-crystallin, play a role in the prevention of protein deposition. Methodolgy/Principal Findings. A series of site-directed mutants of the human molecular chaperone, αB-crystallin, were donstructed 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 αB-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 αB-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 αB-crystallin in regulating its secondary, tertiary and quaternary structure and conferring thermostability to the protein. The capacity to genetically modify αB-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. © 2007 Treweek et al.
Keyword Alzheimer disease
Creutzfeldt Jakob disease
Site-Directed; Mutation
Protein Structure, Quaternary
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
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