Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association
Abstract
Many enveloped viruses encode a matrix protein. In the influenza A virus, the matrix protein M1 polymerizes into a rigid protein layer underneath the viral envelope to help enforce the shape and structural integrity of intact viruses. The influenza virus M1 is also known to mediate virus budding as well as the nuclear export of the viral nucleocapsids and their subsequent packaging into nascent viral particles. Despite extensive studies on the influenza A virus M1 (FLUA-M1), only crystal structures of its N-terminal domain are available. Here we report the crystal structure of the full-length M1 from another orthomyxovirus that infects fish, the infectious salmon anemia virus (ISAV). The structure of ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that of the FLUA-M1. The C domain, which is connected to the N domain through a flexible linker, is made of four α-helices packed as a tight bundle. In the crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions involving both the N and C domains. Results from liposome flotation assays indicated that ISAV-M1 binds membrane via electrostatic interactions that are primarily mediated by a positively charged surface loop from the N domain. Furthemore,more »
- Authors:
-
- Rice Univ., Houston, TX (United States); Huazhong Agricultural Univ., Wuhan (People’s Republic of China)
- Rice Univ., Houston, TX (United States)
- Univ. of Texas Medical School at Houston, TX (United States)
- Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States)
- Huazhong Agricultural Univ., Wuhan (People’s Republic of China)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- Welch Foundation; National Institutes of Health (NIH); National Key Research and Development Program of China; Hamill Foundation; Kresge Science Initiative Endowment Fund
- OSTI Identifier:
- 1438909
- Grant/Contract Number:
- C-1565; AU-1714; AI077785; 2016YFD0500205
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 114; Journal Issue: 32; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; matrix protein; structure; orthomyoxovirus; ISAV; assembly
Citation Formats
Zhang, Wenting, Zheng, Wenjie, Toh, Yukimatsu, Betancourt-Solis, Miguel A., Tu, Jiagang, Fan, Yanlin, Vakharia, Vikram N., Liu, Jun, McNew, James A., Jin, Meilin, and Tao, Yizhi J. Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association. United States: N. p., 2017.
Web. doi:10.1073/pnas.1701747114.
Zhang, Wenting, Zheng, Wenjie, Toh, Yukimatsu, Betancourt-Solis, Miguel A., Tu, Jiagang, Fan, Yanlin, Vakharia, Vikram N., Liu, Jun, McNew, James A., Jin, Meilin, & Tao, Yizhi J. Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association. United States. https://doi.org/10.1073/pnas.1701747114
Zhang, Wenting, Zheng, Wenjie, Toh, Yukimatsu, Betancourt-Solis, Miguel A., Tu, Jiagang, Fan, Yanlin, Vakharia, Vikram N., Liu, Jun, McNew, James A., Jin, Meilin, and Tao, Yizhi J. Mon .
"Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association". United States. https://doi.org/10.1073/pnas.1701747114. https://www.osti.gov/servlets/purl/1438909.
@article{osti_1438909,
title = {Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association},
author = {Zhang, Wenting and Zheng, Wenjie and Toh, Yukimatsu and Betancourt-Solis, Miguel A. and Tu, Jiagang and Fan, Yanlin and Vakharia, Vikram N. and Liu, Jun and McNew, James A. and Jin, Meilin and Tao, Yizhi J.},
abstractNote = {Many enveloped viruses encode a matrix protein. In the influenza A virus, the matrix protein M1 polymerizes into a rigid protein layer underneath the viral envelope to help enforce the shape and structural integrity of intact viruses. The influenza virus M1 is also known to mediate virus budding as well as the nuclear export of the viral nucleocapsids and their subsequent packaging into nascent viral particles. Despite extensive studies on the influenza A virus M1 (FLUA-M1), only crystal structures of its N-terminal domain are available. Here we report the crystal structure of the full-length M1 from another orthomyxovirus that infects fish, the infectious salmon anemia virus (ISAV). The structure of ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that of the FLUA-M1. The C domain, which is connected to the N domain through a flexible linker, is made of four α-helices packed as a tight bundle. In the crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions involving both the N and C domains. Results from liposome flotation assays indicated that ISAV-M1 binds membrane via electrostatic interactions that are primarily mediated by a positively charged surface loop from the N domain. Furthemore, cryoelectron tomography reconstruction of intact ISA virions identified a matrix protein layer adjacent to the inner leaflet of the viral membrane. The physical dimensions of the virion-associated matrix layer are consistent with the 2D ISAV-M1 crystal lattice, suggesting that the crystal lattice is a valid model for studying M1–M1, M1–membrane, and M1–RNP interactions in the virion.},
doi = {10.1073/pnas.1701747114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 32,
volume = 114,
place = {United States},
year = {Mon Jul 24 00:00:00 EDT 2017},
month = {Mon Jul 24 00:00:00 EDT 2017}
}
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