This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rainey-Barger, E. K.
Right arrow Articles by Tsai, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rainey-Barger, E. K.
Right arrow Articles by Tsai, B.

 Previous Article  |  Next Article 

Journal of Virology, February 2009, p. 1483-1491, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02057-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The C-Terminal Domain of ERp29 Mediates Polyomavirus Binding, Unfolding, and Infection{triangledown}

Emily K. Rainey-Barger,1 Souren Mkrtchian,2 and Billy Tsai1*

Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Rm. 3043, Ann Arbor, Michigan 48109,1 Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, 17177 Stockholm, Sweden2

Received 30 September 2008/ Accepted 11 November 2008

Penetration of the endoplasmic reticulum (ER) membrane by polyomavirus (PyV) is a decisive step in virus entry. We showed previously that the ER-resident factor ERp29 induces the local unfolding of PyV to initiate the ER membrane penetration process. ERp29 contains an N-terminal thioredoxin domain (NTD) that mediates its dimerization and a novel C-terminal all-helical domain (CTD) whose function is unclear. The NTD-mediated dimerization of ERp29 is critical for its unfolding activity; whether the CTD plays any role in PyV unfolding is unknown. We now show that three hydrophobic residues within the last helix of the ERp29 CTD that were individually mutated to either lysine or alanine abolished ERp29's ability to stimulate PyV unfolding and infection. This effect was not due to global misfolding of the mutant proteins, as they dimerize and do not form aggregates or display increased protease sensitivity. Moreover, the mutant proteins stimulated secretion of the secretory protein thyroglobulin with an efficiency similar to that of wild-type ERp29. Using a cross-linking coimmunoprecipitation assay, we found that the physical interaction of the ERp29 CTD mutants with PyV is inefficient. Our data thus demonstrate that the ERp29 CTD plays a crucial role in PyV unfolding and infection, likely by serving as part of a substrate-binding domain.

* Corresponding author. Mailing address: Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Rm. 3043, Ann Arbor, MI 48109. Phone: (734) 764-4167. Fax: (734) 764-5155. E-mail: btsai{at}umich.edu

{triangledown} Published ahead of print on 19 November 2008.

Journal of Virology, February 2009, p. 1483-1491, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02057-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Das, S., Smith, T. D., Sarma, J. D., Ritzenthaler, J. D., Maza, J., Kaplan, B. E., Cunningham, L. A., Suaud, L., Hubbard, M. J., Rubenstein, R. C., Koval, M. (2009). ERp29 Restricts Connexin43 Oligomerization in the Endoplasmic Reticulum. Mol. Biol. Cell 20: 2593-2604 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»