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
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by York, J.
Right arrow Articles by Nunberg, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by York, J.
Right arrow Articles by Nunberg, J. H.

 Previous Article  |  Next Article 

Journal of Virology, December 2007, p. 13385-13391, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01785-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Novel Zinc-Binding Domain Is Essential for Formation of the Functional Junín Virus Envelope Glycoprotein Complex{triangledown}

Joanne York and Jack H. Nunberg*

Montana Biotechnology Center, The University of Montana, Missoula, Montana 59812

Received 14 August 2007/ Accepted 25 September 2007

The envelope glycoprotein of the Junín arenavirus (GP-C) mediates entry into target cells through a pH-dependent membrane fusion mechanism. Unlike other class I viral fusion proteins, the mature GP-C complex retains a cleaved, 58-amino-acid signal peptide (SSP) as an essential subunit, required both for trafficking of GP-C to the cell surface and for the activation of membrane fusion. SSP has been shown to associate noncovalently in GP-C via the cytoplasmic domain (CTD) of the transmembrane fusion subunit G2. In this report we investigate the molecular basis for this intersubunit interaction. We identify an invariant series of six cysteine and histidine residues in the CTD of G2 that is essential for incorporation of SSP in the GP-C complex. Moreover, we show that a CTD peptide fragment containing His-447, His-449, and Cys-455 specifically binds Zn2+ at subnanomolar concentrations. Together, these results suggest a zinc finger-like domain structure in the CTD of G2. We propose that the remaining residues in the series (His-459, Cys-467, and Cys-469) form an intersubunit zinc-binding center that incorporates Cys-57 of SSP. This unusual motif may act to retain SSP in the GP-C complex and position the ectodomain loop of SSP for its role in modulating membrane fusion activity. The unique tripartite organization of GP-C could provide novel molecular targets for therapeutic intervention in arenaviral disease.

* Corresponding author. Mailing address: Montana Biotechnology Center, The University of Montana, Science Complex, Room 221, Missoula, MT 59812. Phone: (406) 243-6421. Fax: (406) 243-6425. E-mail: jack.nunberg{at}umontana.edu

{triangledown} Published ahead of print on 10 October 2007.

Journal of Virology, December 2007, p. 13385-13391, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01785-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Agnihothram, S. S., Dancho, B., Grant, K. W., Grimes, M. L., Lyles, D. S., Nunberg, J. H. (2009). Assembly of Arenavirus Envelope Glycoprotein GPC in Detergent-Soluble Membrane Microdomains. J. Virol. 83: 9890-9900 [Abstract] [Full Text]  
  • York, J., Nunberg, J. H. (2009). Intersubunit Interactions Modulate pH-Induced Activation of Membrane Fusion by the Junin Virus Envelope Glycoprotein GPC. J. Virol. 83: 4121-4126 [Abstract] [Full Text]  
  • Larson, R. A., Dai, D., Hosack, V. T., Tan, Y., Bolken, T. C., Hruby, D. E., Amberg, S. M. (2008). Identification of a Broad-Spectrum Arenavirus Entry Inhibitor. J. Virol. 82: 10768-10775 [Abstract] [Full Text]  
  • York, J., Dai, D., Amberg, S. M., Nunberg, J. H. (2008). pH-Induced Activation of Arenavirus Membrane Fusion Is Antagonized by Small-Molecule Inhibitors. J. Virol. 82: 10932-10939 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»