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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]  


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