1. The Viral Class II Membrane Fusion Machinery: Divergent Evolution from an Ancestral Heterodimer
- Author
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Pablo Guardado-Calvo, Félix A. Rey, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This research was funded by ANR, grant number ANR-18-CE11-0011, and Labex IBEID, grant number ANR-10-LABX-62-IBEID., ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
- Subjects
Conformational change ,Bunyaviridae ,Lipid Bilayers ,Alphavirus ,Review ,bunyavirus ,Genome, Viral ,Microbiology ,03 medical and health sciences ,Viral envelope ,Virology ,Animals ,Humans ,Lipid bilayer ,class II fusion proteins ,030304 developmental biology ,Glycoproteins ,chemistry.chemical_classification ,0303 health sciences ,structural homology ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,biology ,030306 microbiology ,Chemistry ,Membrane fusion protein ,Virion ,Lipid bilayer fusion ,Virus Internalization ,biology.organism_classification ,Biological Evolution ,QR1-502 ,Cell biology ,Divergent evolution ,Models, Structural ,Infectious Diseases ,Protein Multimerization ,Glycoprotein ,Viral Fusion Proteins - Abstract
International audience; A key step during the entry of enveloped viruses into cells is the merger of viral and cell lipid bilayers. This process is driven by a dedicated membrane fusion protein (MFP) present at the virion surface, which undergoes a membrane–fusogenic conformational change triggered by interactions with the target cell. Viral MFPs have been extensively studied structurally, and are divided into three classes depending on their three-dimensional fold. Because MFPs of the same class are found in otherwise unrelated viruses, their intra-class structural homology indicates horizontal gene exchange. We focus this review on the class II fusion machinery, which is composed of two glycoproteins that associate as heterodimers. They fold together in the ER of infected cells such that the MFP adopts a conformation primed to react to specific clues only upon contact with a target cell, avoiding premature fusion in the producer cell. We show that, despite having diverged in their 3D fold during evolution much more than the actual MFP, the class II accompanying proteins (AP) also derive from a distant common ancestor, displaying an invariant core formed by a β-ribbon and a C-terminal immunoglobulin-like domain playing different functional roles—heterotypic interactions with the MFP, and homotypic AP/AP contacts to form spikes, respectively. Our analysis shows that class II APs are easily identifiable with modern structural prediction algorithms, providing useful information in devising immunogens for vaccine design.
- Published
- 2021
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