Structural Characterization of the glycoprotein GP2 Core Domain from the CAS Virus, a Novel Arenavirus-like Species

By J. Koellhoffer, Z. Dai, V. Malashkevich, M. Stenglein, Yanyun Liu, R. Toro, Joseph S. Harrison, K. Chandran, J. Derisi, S. Almo and 1 more. Journal of Molecular Biology, 2013

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Fusion of the viral and host cell membranes is a necessary first step for infection by enveloped viruses, and is mediated by the envelope glycoprotein. The transmembrane subunits from the structurally defined “class I” glycoproteins adopt an α-helical “trimer- of-hairpins” conformation during the fusion pathway. Here we present our studies on the envelope glycoprotein transmembrane subunit, GP2, of the CAS virus (CASV). CASV was recently identified from annulated tree boas (Corallus annulatus) with inclusion body disease and is implicated in the disease etiology. We have generated and characterized two protein constructs consisting of the predicted CASV GP2 core domain. The crystal structure of the CASV GP2 post-fusion conformation indicates a trimeric α-helical bundle that is highly similar to those of Ebola Virus (EBOV) and Marburg Virus (MARV) GP2, despite CASV genome homology to arenaviruses. Denaturation studies demonstrate that the stability of CASV GP2 is pH-dependent with higher stability at lower pH; we propose that this behavior is due to a network of interactions among acidic residues that would destabilize the α-helical bundle under conditions where the side chains are deprotonated. The pH-dependent stability of the post-fusion structure has been observed in EBOV and MARV GP2, as well as other viruses that enter via the endosome. Infection experiments with CASV and the related Golden Gate Virus (GGV) support a mechanism of entry that requires endosomal acidification. Our results suggest that despite being primarily arenavirus-like, the transmembrane subunit of CASV is extremely similar to the filoviruses.

Subfields: Epidemiology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d2a5e8127e65f86418503e897210a5e02ecbd2e1

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