Enhanced Fusion Pore Expansion Mediated by the Trans-Acting Endodomain of the Reovirus FAST Proteins

PLoS Pathogens

Deniz Top¹  Trina Racine¹  Chelsey Louise Ellis¹  Chris Barry¹ 

[1] Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

关键词: Membrane fusion;    Cell fusion;    Membrane proteins;    Integral membrane proteins;    Plasmid construction;    Viral entry;    Sequence motif analysis;    Alanine;   

DOI  :  10.1371/journal.ppat.1000331

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell–cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of the endodomains of the p10, p14, and p15 FAST proteins enhances syncytiogenesis induced by the full-length FAST proteins, both homotypically and heterotypically. Results further indicate that the 68-residue cytoplasmic endodomain of the p14 FAST protein (1) is endogenously generated from full-length p14 protein expressed in virus-infected or transfected cells; (2) enhances syncytiogenesis subsequent to stable pore formation; (3) increases the syncytiogenic activity of heterologous fusion proteins, including the differentiation-dependent fusion of murine myoblasts; (4) exerts its enhancing activity from the cytosol, independent of direct interactions with either the fusogen or the membranes being fused; and (5) contains several regions with protein–protein interaction motifs that influence enhancing activity. We propose that the unique evolution of the FAST proteins as virus-encoded cellular fusogens has allowed them to generate a trans-acting, soluble endodomain peptide to harness a cellular pathway or process involved in the poorly understood process that facilitates the transition from microfusion pores to macrofusion and syncytiogenesis.

【 授权许可】

CC BY