Vaccinia viral A26 protein is a fusion suppressor of mature virus and triggers membrane fusion through conformational change at low pH

• DOI: 10.1371/journal.ppat.1007826
• Publication Date: 2019-06-20T17:46:41Z
• Authors: Hung-Wei Chang; Cheng-Han Yang; Yu-Chun Luo; Bo-Gang Su; Huei-Yin Cheng; Shu-Yun Tung; Kathleen Joyce D....; Yi-Ting Liao; Der-Lii M. Tzou; Hao-Ching Wang; Wen Chang
• Keywords: Cell fusion

Vaccinia mature virus requires A26 envelope protein to mediate acid-dependent endocytosis into HeLa cells in which we hypothesized that functions as an acid-sensitive membrane fusion suppressor. Here, provide evidence showing N-terminal domain (aa1-75) of is region regulates fusion. Crystal structure revealed His48 and His53 are close contact with Lys47, Arg57, His314 Arg312, suggesting at low pH these His-cation pairs could initiate conformational changes through protonation subsequent electrostatic repulsion. All the mutant viruses interrupted pair interactions His 53 indeed have lost virion infectivity. Isolation revertant second site mutations caused frame shifts premature termination such reverent regained cell entry plasma Together, conclude viral suppressor during vaccinia endocytosis.