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Capsid protein structure in Zika virus reveals the flavivirus assembly process.
Nat Commun. 2020 Feb 14; 11(1):895.NC

Abstract

Structures of flavivirus (dengue virus and Zika virus) particles are known to near-atomic resolution and show detailed structure and arrangement of their surface proteins (E and prM in immature virus or M in mature virus). By contrast, the arrangement of the capsid proteins:RNA complex, which forms the core of the particle, is poorly understood, likely due to inherent dynamics. Here, we stabilize immature Zika virus via an antibody that binds across the E and prM proteins, resulting in a subnanometer resolution structure of capsid proteins within the virus particle. Fitting of the capsid protein into densities shows the presence of a helix previously thought to be removed via proteolysis. This structure illuminates capsid protein quaternary organization, including its orientation relative to the lipid membrane and the genomic RNA, and its interactions with the transmembrane regions of the surface proteins. Results show the capsid protein plays a central role in the flavivirus assembly process.

Authors+Show Affiliations

Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Department of Biological Sciences, National University of Singapore, Singapore, 117558, Singapore.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.CryoEM Unit, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore.Department of Biochemistry and Molecular Biology, Sealy Center for Structural and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, 77555-0647, USA.Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., CH-6500, Bellinzona, Switzerland.Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. sheemei.lok@duke-nus.edu.sg. Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore, 117557, Singapore. sheemei.lok@duke-nus.edu.sg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32060358

Citation

Tan, Ter Yong, et al. "Capsid Protein Structure in Zika Virus Reveals the Flavivirus Assembly Process." Nature Communications, vol. 11, no. 1, 2020, p. 895.
Tan TY, Fibriansah G, Kostyuchenko VA, et al. Capsid protein structure in Zika virus reveals the flavivirus assembly process. Nat Commun. 2020;11(1):895.
Tan, T. Y., Fibriansah, G., Kostyuchenko, V. A., Ng, T. S., Lim, X. X., Zhang, S., Lim, X. N., Wang, J., Shi, J., Morais, M. C., Corti, D., & Lok, S. M. (2020). Capsid protein structure in Zika virus reveals the flavivirus assembly process. Nature Communications, 11(1), 895. https://doi.org/10.1038/s41467-020-14647-9
Tan TY, et al. Capsid Protein Structure in Zika Virus Reveals the Flavivirus Assembly Process. Nat Commun. 2020 Feb 14;11(1):895. PubMed PMID: 32060358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Capsid protein structure in Zika virus reveals the flavivirus assembly process. AU - Tan,Ter Yong, AU - Fibriansah,Guntur, AU - Kostyuchenko,Victor A, AU - Ng,Thiam-Seng, AU - Lim,Xin-Xiang, AU - Zhang,Shuijun, AU - Lim,Xin-Ni, AU - Wang,Jiaqi, AU - Shi,Jian, AU - Morais,Marc C, AU - Corti,Davide, AU - Lok,Shee-Mei, Y1 - 2020/02/14/ PY - 2019/05/20/received PY - 2020/01/18/accepted PY - 2020/2/16/entrez PY - 2020/2/16/pubmed PY - 2020/2/16/medline SP - 895 EP - 895 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - Structures of flavivirus (dengue virus and Zika virus) particles are known to near-atomic resolution and show detailed structure and arrangement of their surface proteins (E and prM in immature virus or M in mature virus). By contrast, the arrangement of the capsid proteins:RNA complex, which forms the core of the particle, is poorly understood, likely due to inherent dynamics. Here, we stabilize immature Zika virus via an antibody that binds across the E and prM proteins, resulting in a subnanometer resolution structure of capsid proteins within the virus particle. Fitting of the capsid protein into densities shows the presence of a helix previously thought to be removed via proteolysis. This structure illuminates capsid protein quaternary organization, including its orientation relative to the lipid membrane and the genomic RNA, and its interactions with the transmembrane regions of the surface proteins. Results show the capsid protein plays a central role in the flavivirus assembly process. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/32060358/Capsid_protein_structure_in_Zika_virus_reveals_the_flavivirus_assembly_process L2 - http://dx.doi.org/10.1038/s41467-020-14647-9 DB - PRIME DP - Unbound Medicine ER -
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