title: Structural characterization of the glycoprotein GP2 core domain from the CAS virus, a novel arenavirus-like species.
abstract: 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 and Marburg virus 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 Ebola virus and Marburg virus GP2, as well as other viruses that enter via the endosome. Infection experiments with CASV and the related Golden Gate virus 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.
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Jayne F
authors: JF
authors: Koellhoffer
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Zhou
authors: Z
authors: Dai
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Vladimir N
authors: VN
authors: Malashkevich
authors: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158-2517, USA.
authors: Mark D
authors: MD
authors: Stenglein
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Yanyun
authors: Y
authors: Liu
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Rafael
authors: R
authors: Toro
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Joseph
authors: J
authors: S Harrison
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Kartik
authors: K
authors: Chandran
authors: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158-2517, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
authors: Joseph L
authors: JL
authors: DeRisi
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors: Steven C
authors: SC
authors: Almo
authors: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Electronic address: jon.lai@einstein.yu.edu.
authors: Jonathan R
authors: JR
authors: Lai
mesh_terms: D000595:Amino Acid Sequence; D018050:Arenavirus / Q000378:metabolism*; D029043:Ebolavirus / Q000378:metabolism; D007797:Laminin / Q000737:chemistry*; D008969:Molecular Sequence Data
chemical_list: D007797:Laminin
keywords: arenavirus; filovirus; inclusion body disease; viral membrane fusion