Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes)

Courtney E Garry,Robert F Garry

doi:10.1186/1742-4682-1-10

Courtney E Garry, Robert F Garry

Open Access

https://doi.org/10.1186/1742-4682-1-10

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Journal: Theoretical biology & medical modelling	Publication Date: Jan 1, 2004
Citations: 159	License type: cc-by

Affiliation: Tulane University

Abstract

The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes), encoded by members of the Alphaviridae and Flaviviridae, are comprised of three antiparallel beta sheet domains with an internal fusion peptide located at the end of domain II. Proteomics computational analyses indicate that the carboxyl terminal glycoprotein (Gc) encoded by Sandfly fever virus (SAN), a phlebovirus, has a significant amino acid sequence similarity with envelope protein 1 (E1), the class II fusion protein of Sindbis virus (SIN), an Alphavirus. Similar sequences and common structural/functional motifs, including domains with a high propensity to interface with bilayer membranes, are located collinearly in SAN Gc and SIN E1. Gc encoded by members of each Bunyavirus genus share several sequence and structural motifs. These results suggest that Gc of Bunyaviridae, and similar proteins of Tenuiviruses and a group of Caenorhabditis elegans retroviruses, are class II viral fusion proteins. Comparisons of divergent viral fusion proteins can reveal features essential for virion:cell fusion, and suggest drug and vaccine strategies.

Highlights

Two classes of viral envelope proteins that mediate virion:cell fusion have been described
Gallaher [1] fit the fusion protein of Ebola virus, a filovirus, to retroviral transmembrane glycoprotein (TM). Both models proved remarkably similar to the structures of these fusion proteins solved later by Xray crystallography [27,28,29]. These results indicate that Gallaher's "Rosetta Stone" strategy, which employs the fusion peptide and other identifiable features in combination with computer algorithms that predict secondary structure, is a useful approach to the construction of working models of class I viral fusion proteins
Proteomics computational analyses suggest that Bunyavirus Gc proteins are class II viral fusion proteins (β-penetrenes), with a structure similar to the fusion proteins of Alphaviruses and Flaviviruses

Summary

Introduction

Two classes of viral envelope proteins that mediate virion:cell fusion have been described. Class I and II fusion proteins (aka α-and β-penetrenes) are distinguished, in part, by the location of the "fusion peptide," a cluster of hydrophobic and aromatic amino acids that appears critical for fusing viral and cell membranes. The overall structures of these two classes of viral fusions proteins are distinct. Several otherwise disparate viruses, including orthomyxoviruses, paramyxoviruses, retroviruses, arenaviruses, filoviruses and coronaviruses encode class I fusion proteins [1,2,3,4]. Class II fusion proteins are comprised mostly of antiparallel β sheets. The prototypic class II fusion protein is the E glycoprotein of tick-borne encephalitis virus (TBEV), a (page number not for citation purposes)

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