A Compact, Multifunctional Fusion Module Directs Cholesterol-Dependent Homomultimerization and Syncytiogenic Efficiency of Reovirus p10 FAST Proteins

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Natural infections by fusogenic orthoreoviruses can result in severe afflictions ranging from neuropathogenicity to pneumonia and death. The fusogenic capacity of these viruses, attributable to a unique family of fusion-associated small transmembrane (FAST) proteins, is a correlate of virulence. The FAST proteins are the only known examples of nonenveloped virus membrane fusion proteins, and they are the smallest known viral fusogens whose structural and functional attributes are incompatible with current models of protein-mediated membrane fusion. Exploiting the sequence divergence and distinct syncytiogenic rates of representative p10 FAST proteins from avian and bat reovirus isolates, we determined the p10 ectodomain is a compact, complex fusion module comprising two independent functional motifs. One motif determines species-specific p10 fusion efficiency by governing formation of a cystine loop fusion peptide, while the other directs reversible clustering and multimerization of p10 in cholesterol-dependent membrane microdomains. Remarkably, a juxtamembrane tetra-peptide is solely responsible for co-dependent clustering and multimerization of p10 in distinct, species-specific fusion platforms. This is the first example of a viral fusogen utilizing a membrane-proximal ectodomain region (MPER) to direct cholesterol-dependent multimerization and assembly into fusion platforms.

Vyšlo v časopise: A Compact, Multifunctional Fusion Module Directs Cholesterol-Dependent Homomultimerization and Syncytiogenic Efficiency of Reovirus p10 FAST Proteins. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004023
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004023

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