MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
MCB.02127-06v1
27/15/5445    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tank, E. M. H.
Right arrow Articles by True, H. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tank, E. M. H.
Right arrow Articles by True, H. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2007, p. 5445-5455, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.02127-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prion Protein Repeat Expansion Results in Increased Aggregation and Reveals Phenotypic Variability{triangledown}

Elizabeth M. H. Tank, David A. Harris, Amar A. Desai, and Heather L. True*

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

Received 14 November 2006/ Returned for modification 22 January 2007/ Accepted 21 May 2007

Mammalian prion diseases are fatal neurodegenerative disorders dependent on the prion protein PrP. Expansion of the oligopeptide repeats (ORE) found in PrP is associated with inherited prion diseases. Patients with ORE frequently harbor PrP aggregates, but other factors may contribute to pathology, as they often present with unexplained phenotypic variability. We created chimeric yeast-mammalian prion proteins to examine the influence of the PrP ORE on prion properties in yeast. Remarkably, all chimeric proteins maintained prion characteristics. The largest repeat expansion chimera displayed a higher propensity to maintain a self-propagating aggregated state. Strikingly, the repeat expansion conferred increased conformational flexibility, as observed by enhanced phenotypic variation. Furthermore, the repeat expansion chimera displayed an increased rate of prion conversion, but only in the presence of another aggregate, the [RNQ+] prion. We suggest that the PrP ORE increases the conformational flexibility of the prion protein, thereby enhancing the formation of multiple distinct aggregate structures and allowing more frequent prion conversion. Both of these characteristics may contribute to the phenotypic variability associated with PrP repeat expansion diseases.

* Corresponding author. Mailing address: Department of Cell Biology and Physiology, Washington University School of Medicine, Campus Box 8228, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-3934. Fax: (314) 362-7463. E-mail: htrue{at}cellbiology.wustl.edu

{triangledown} Published ahead of print on 4 June 2007.

Molecular and Cellular Biology, August 2007, p. 5445-5455, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.02127-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2007 by the American Society for Microbiology. All rights reserved.