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

Hung Wei Chang, Cheng Han Yang, Yu Chun Luo, Bo Gang Su, Huei Yin Cheng, Shu Yun Tung, Kathleen Joyce D. Carillo, Yi Ting Liao, Der Lii M. Tzou, Hao Ching Wang, Wen Chang

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Article numbere1007826
JournalPLoS Pathogens
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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faropenem medoxomil
Vaccinia
Virus Internalization
Viral Proteins
Membrane Fusion
Acids
Vaccinia virus
Endocytosis
Viruses
Proteins
Cations
Frameshift Mutation
Static Electricity
HeLa Cells
Virion
Cell Membrane

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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Vaccinia viral A26 protein is a fusion suppressor of mature virus and triggers membrane fusion through conformational change at low pH. / Chang, Hung Wei; Yang, Cheng Han; Luo, Yu Chun; Su, Bo Gang; Cheng, Huei Yin; Tung, Shu Yun; Carillo, Kathleen Joyce D.; Liao, Yi Ting; Tzou, Der Lii M.; Wang, Hao Ching; Chang, Wen.

In: PLoS Pathogens, Vol. 15, No. 6, e1007826, 01.06.2019.

Research output: Contribution to journalArticle

Chang, HW, Yang, CH, Luo, YC, Su, BG, Cheng, HY, Tung, SY, Carillo, KJD, Liao, YT, Tzou, DLM, Wang, HC & Chang, W 2019, 'Vaccinia viral A26 protein is a fusion suppressor of mature virus and triggers membrane fusion through conformational change at low pH', PLoS Pathogens, vol. 15, no. 6, e1007826. https://doi.org/10.1371/journal.ppat.1007826
Chang, Hung Wei ; Yang, Cheng Han ; Luo, Yu Chun ; Su, Bo Gang ; Cheng, Huei Yin ; Tung, Shu Yun ; Carillo, Kathleen Joyce D. ; Liao, Yi Ting ; Tzou, Der Lii M. ; Wang, Hao Ching ; Chang, Wen. / Vaccinia viral A26 protein is a fusion suppressor of mature virus and triggers membrane fusion through conformational change at low pH. In: PLoS Pathogens. 2019 ; Vol. 15, No. 6.
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