Structure of a zinc-binding domain in the Junin virus envelope glycoprotein.
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.
Department of Chemistry and Biochemistry, University of Montana, Missoula, Montana 59812, USA. klara.briknarova@umontana.edu
Klára
K
Briknarová
Celestine J
CJ
Thomas
Joanne
J
York
Jack H
JH
Nunberg
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D006863:Hydrogen-Ion Concentration; D018051:Junin virus / Q000737:chemistry* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology
C555941:GPC protein, junin virus; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; D015032:Zinc