Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH-Sensor [Microbiology]

June 16th, 2015 by Cook, J. D., Soto-Montoya, H., Korpela, M. K., Lee, J. E.

Segment 5, open reading frame (ORF) 1 of the infectious salmon anemia virus (ISAV) genome encodes for the ISAV F protein, which is responsible for viral-host endosomal membrane fusion during a productive ISAV infection. The entry machinery of ISAV is comprised of a complex of the ISAV F and ISAV HE proteins in an unknown stoichiometry prior to receptor engagement by ISAV HE. Following binding of the receptor to ISAV HE, dissociation of the ISAV F protein from HE and subsequent endocytosis, the ISAV F protein resolves into a fusion competent oligomeric state. Here, we present a 2.1 Å crystal structure of the fusion core of the ISAV F protein solved at low pH. This structure has allowed us to unambiguously demonstrate that the ISAV entry machinery exhibits typical Class I viral fusion protein architecture. Furthermore, we have determined stabilizing factors that accommodate the pH-dependent mode of ISAV transmission and our structure has allowed the identification of a central coil that is conserved across numerous and varied post-fusion viral glycoprotein structures. We then discuss a mechanistic model of ISAV fusion that parallels the paramyxoviral Class I fusion strategy wherein attachment and fusion are relegated to separate proteins in a similar fashion to ISAV fusion.
  • Posted in Journal of Biological Chemistry, Publications
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