Journal of Biological Chemistry
Volume 286, Issue 2, 14 January 2011, Pages 1528-1536
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Protein Structure and Folding
Structure of a Zinc-binding Domain in the Junín Virus Envelope Glycoprotein*

https://doi.org/10.1074/jbc.M110.166025Get rights and content
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Arenaviruses cause acute hemorrhagic fevers with high mortality. Entry of the virus into the host cell is mediated by the viral envelope glycoprotein, GPC. In contrast to other class I viral envelope glycoproteins, the mature GPC complex contains a cleaved stable signal peptide (SSP) in addition to the canonical receptor-binding (G1) and transmembrane fusion (G2) subunits. SSP is critical for intracellular transport of the GPC complex to the cell surface and for its membrane-fusion activity. Previous studies have suggested that SSP is retained in GPC through interaction with a zinc-binding domain (ZBD) in the cytoplasmic tail of G2. Here we used NMR spectroscopy to determine the structure of Junín virus (JUNV) ZBD (G2 residues 445–485) and investigate its interaction with a conserved Cys residue (Cys-57) in SSP. We show that JUNV ZBD displays a novel fold containing two zinc ions. One zinc ion is coordinated by His-447, His-449, Cys-455, and His-485. The second zinc ion is coordinated by His-459, Cys-467, and Cys-469 and readily accepts Cys-57 from SSP as the fourth ligand. Our studies describe the structural basis for retention of the unique SSP subunit and suggest a mechanism whereby SSP is positioned in the GPC complex to modulate pH-dependent membrane fusion.

NMR
Protein Structure
Protein-Protein Interactions
Viral Protein
Zinc finger
GPC
Arenavirus
Junin Virus
Virus Envelope Glycoprotein
Zinc-binding Domain

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The atomic coordinates and structure factors (code 2LOZ) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

*

This work was supported by National Institutes of Health Research Grant R01 AI074818 (to J. H. N.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S10 and Table S1.