Unknown

Dataset Information

0

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


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.

SUBMITTER: Chang HW 

PROVIDER: S-EPMC6605681 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Chang Hung-Wei HW   Yang Cheng-Han CH   Luo Yu-Chun YC   Su Bo-Gang BG   Cheng Huei-Yin HY   Tung Shu-Yun SY   Carillo Kathleen Joyce D KJD   Liao Yi-Ting YT   Tzou Der-Lii M DM   Wang Hao-Ching HC   Chang Wen W  

PLoS pathogens 20190620 6


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 thes  ...[more]

Similar Datasets

| S-EPMC5309949 | biostudies-other
| S-EPMC5700061 | biostudies-literature
| S-EPMC2698572 | biostudies-literature
| S-EPMC3701885 | biostudies-literature
| S-EPMC5571262 | biostudies-literature
| S-EPMC3749956 | biostudies-literature
| S-EPMC4249083 | biostudies-literature
| S-EPMC9877100 | biostudies-literature
| S-EPMC4811418 | biostudies-literature
| S-EPMC1395410 | biostudies-literature