ABSTRACT
Here, we announce the predicted structures of the 193 proteins encoded by African swine fever virus (ASFV) strain Georgia 2007 (ASFV-G). Previously, only the structures of 16 ASFV proteins were elucidated.
ANNOUNCEMENT
African swine fever (ASF) is a highly infectious and fatal disease of feral and domesticated swine that is the only member of the family Asfarviridae and genus Asfivirus. ASF has spread through several Eurasian countries and, more recently, has reappeared for the first time in over 40 years in the Western Hemisphere, with a positive identification in the Dominican Republic (1). Currently, only the structures of 16 of the nearly 200 predicted ASF virus (ASFV) proteins have been solved via X-ray diffraction, solution nuclear magnetic resonance (NMR), or electron microscopy and are hosted as 52 Protein Data Bank (PDB) files by the Research Collaboratory for Structural Bioinformatics (2–19). In the 14th Critical Assessment of Protein Structure, AlphaFold was determined to demonstrate protein structure accuracy comparable to experimentally resolved structures (20). Accordingly, the structures of all 193 proteins predicted to be encoded by the progenitor strain from the most recent outbreak, ASFV Georgia 2007 (ASFV-G) (GenBank accession number FR682468), were determined using AlphaFold (21). Utilizing the U.S. Department of Agriculture’s (USDA) Agricultural Research Service (ARS) Scientific Computing Initiative (SCINet) Ceres high-performance computing (HPC) cluster or the SCINet/Mississippi State University (MSU) collaborative Atlas HPC cluster, structural predictions were performed for all proteins (except QP509L) by running AlphaFold v2.2.0 using the default databases and the following parameters: model_preset = monomer, db_preset = full_dbs, use_gpu_relax = True, max_template_date = 2020-05-14. Due to hardware limitations, QP509L was instead predicted using the AlphaFold v2.1.0 colab notebook without run relaxation or homologous structures and using a reduced Big Fantastic Database (BFD) (20). The unrelaxed model was then minimized and subjected to molecular dynamics for 1 ns using GROMACS (22–26). The per-residue estimate of confidence (pLDDT) generated using AlphaFold is included in each structure file. The predicted protein structures are essential for the in silico prediction of B-cell and T-cell epitopes and the development of antivirals.
Data availability.
All PDB structure files can be found on the download page at the website for the Center of Excellence for African Swine Fever Genomics (https://asfvgenomics.com/) or in ModelArchive at https://modelarchive.org/doi/10.5452/ma-asfv-asfvg. Individual ASFV protein structural predictions can also be found in Table 1.
TABLE 1.
Predicted structures of the 193 proteins encoded by ASFV strain Georgia 2007
ACKNOWLEDGMENTS
This work was supported by research funded by the U.S. Department of Agriculture, Agricultural Research Service (ARS)-CRIS project 1940-32000-063-00D. This research used resources provided by the SCINet project and the AI Center of Excellence of the USDA Agricultural Research Service (ARS project number 0500-00093-001-00-D). We thank the SCINet Virtual Research Support Core (VRSC) in Ames, IA, for hosting the Ceres HPC cluster and the collaboration between MSU and the U.S. Department of Agriculture’s Agricultural Research Service for hosting the Atlas HPC cluster.
Contributor Information
Manuel V. Borca, Email: Manuel.Borca@usda.gov.
Douglas P. Gladue, Email: Douglas.Gladue@usda.gov.
Kenneth M. Stedman, Portland State University
REFERENCES
- 1.Gonzales W, Moreno C, Duran U, Henao N, Bencosme M, Lora P, Reyes R, Nunez R, De Gracia A, Perez AM. 2021. African swine fever in the Dominican Republic. Transbound Emerg Dis 68:3018–3019. doi: 10.1111/tbed.14341. [DOI] [PubMed] [Google Scholar]
- 2.Banjara S, Caria S, Dixon LK, Hinds MG, Kvansakul M. 2017. Structural insight into African swine fever virus A179L-mediated inhibition of apoptosis. J Virol 91:e02228-16. doi: 10.1128/JVI.02228-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Banjara S, Shimmon GL, Dixon LK, Netherton CL, Hinds MG, Kvansakul M. 2019. Crystal structure of African swine fever virus A179L with the autophagy regulator Beclin. Viruses 11:789. doi: 10.3390/v11090789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Chen Y, Chen X, Huang Q, Shao Z, Gao Y, Li Y, Yang C, Liu H, Li J, Wang Q, Ma J, Zhang Y-Z, Gu Y, Gan J. 2020. A unique DNA-binding mode of African swine fever virus AP endonuclease. Cell Discov 6:13. doi: 10.1038/s41421-020-0146-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Chen Y, Liu H, Yang C, Gao Y, Yu X, Chen X, Cui R, Zheng L, Li S, Li X, Ma J, Huang Z, Li J, Gan J. 2019. Structure of the error-prone DNA ligase of African swine fever virus identifies critical active site residues. Nat Commun 10:387. doi: 10.1038/s41467-019-08296-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Du X, Gao Z-Q, Geng Z, Dong Y-H, Zhang H. 2021. Structure and biochemical characteristic of the methyltransferase (MTase) domain of RNA capping enzyme from African swine fever virus. J Virol 95:e02029-20. doi: 10.1128/JVI.02029-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Guo F, Shi Y, Yang M, Guo Y, Shen Z, Li M, Chen Y, Liang R, Yang Y, Chen H, Peng G. 2021. The structural basis of African swine fever virus core shell protein p15 binding to DNA. FASEB J 35:e21350. doi: 10.1096/fj.202002145R. [DOI] [PubMed] [Google Scholar]
- 8.Hakim M, Fass D. 2009. Dimer interface migration in a viral sulfhydryl oxidase. J Mol Biol 391:758–768. doi: 10.1016/j.jmb.2009.06.070. [DOI] [PubMed] [Google Scholar]
- 9.Huang J-W, Niu D, Liu K, Wang Q, Ma L, Chen C-C, Zhang L, Liu W, Zhou S, Min J, Wu S, Yang Y, Guo R-T. 2020. Structure basis of non-structural protein pA151R from African swine fever virus. Biochem Biophys Res Commun 532:108–113. doi: 10.1016/j.bbrc.2020.08.011. [DOI] [PubMed] [Google Scholar]
- 10.Li C, Chai Y, Song H, Weng C, Qi J, Sun Y, Gao GF. 2019. Crystal structure of African swine fever virus dUTPase reveals a potential drug target. mBio 10:e02483-19. doi: 10.1128/mBio.02483-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Li G, Fu D, Zhang G, Zhao D, Li M, Geng X, Sun D, Wang Y, Chen C, Jiao P, Cao L, Guo Y, Rao Z. 2020. Crystal structure of the African swine fever virus structural protein p35 reveals its role for core shell assembly. Protein Cell 11:600–605. doi: 10.1007/s13238-020-00730-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Li G, Liu X, Yang M, Zhang G, Wang Z, Guo K, Gao Y, Jiao P, Sun J, Chen C, Wang H, Deng W, Xiao H, Li S, Wu H, Wang Y, Cao L, Jia Z, Shang L, Yang C, Guo Y, Rao Z. 2020. Crystal structure of African swine fever virus pS273R protease and implications for inhibitor design. J Virol 94:e02125-19. doi: 10.1128/JVI.02125-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Li G, Wang C, Yang M, Cao L, Fu D, Liu X, Sun D, Chen C, Wang Y, Jia Z, Yang C, Guo Y, Rao Z. 2020. Structural insight into African swine fever virus dUTPase reveals a novel folding pattern in the dUTPase family. J Virol 94:e01698-19. doi: 10.1128/JVI.01698-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Liang R, Wang G, Zhang D, Ye G, Li M, Shi Y, Shi J, Chen H, Peng G. 2021. Structural comparisons of host and African swine fever virus dUTPases reveal new clues for inhibitor development. J Biol Chem 296:100015. doi: 10.1074/jbc.RA120.014005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Liu Q, Ma B, Qian N, Zhang F, Tan X, Lei J, Xiang Y. 2019. Structure of the African swine fever virus major capsid protein p72. Cell Res 29:953–955. doi: 10.1038/s41422-019-0232-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Liu R, Sun Y, Chai Y, Li S, Li S, Wang L, Su J, Yu S, Yan J, Gao F, Zhang G, Qiu H-J, Gao GF, Qi J, Wang H. 2020. The structural basis of African swine fever virus pA104R binding to DNA and its inhibition by stilbene derivatives. Proc Natl Acad Sci USA 117:11000–11009. doi: 10.1073/pnas.1922523117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Maciejewski MW, Shin R, Pan B, Marintchev A, Denninger A, Mullen MA, Chen K, Gryk MR, Mullen GP. 2001. Solution structure of a viral DNA repair polymerase. Nat Struct Biol 8:936–941. doi: 10.1038/nsb1101-936. [DOI] [PubMed] [Google Scholar]
- 18.Showalter AK, Byeon IJ, Su MI, Tsai MD. 2001. Solution structure of a viral DNA polymerase X and evidence for a mutagenic function. Nat Struct Biol 8:942–946. doi: 10.1038/nsb1101-942. [DOI] [PubMed] [Google Scholar]
- 19.Wu W-J, Su M-I, Wu J-L, Kumar S, Lim L-H, Wang C-WE, Nelissen FHT, Chen M-CC, Doreleijers JF, Wijmenga SS, Tsai M-D. 2014. How a low-fidelity DNA polymerase chooses non-Watson-Crick from Watson-Crick incorporation. J Am Chem Soc 136:4927–4937. doi: 10.1021/ja4102375. [DOI] [PubMed] [Google Scholar]
- 20.Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D. 2021. Highly accurate protein structure prediction with AlphaFold. Nature 596:583–589. doi: 10.1038/s41586-021-03819-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Chapman DA, Darby AC, Da Silva M, Upton C, Radford AD, Dixon LK. 2011. Genomic analysis of highly virulent Georgia 2007/1 isolate of African swine fever virus. Emerg Infect Dis 17:599–605. doi: 10.3201/eid1704.101283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Berendsen HJC, van der Spoel D, van Drunen R. 1995. GROMACS—a message-passing parallel molecular-dynamics implementation. Comput Phys Commun 91:43–56. doi: 10.1016/0010-4655(95)00042-E. [DOI] [Google Scholar]
- 23.Lindahl E, Hess B, van der Spoel D. 2001. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7:306–317. doi: 10.1007/s008940100045. [DOI] [Google Scholar]
- 24.Van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC. 2005. GROMACS: fast, flexible, and free. J Comput Chem 26:1701–1718. doi: 10.1002/jcc.20291. [DOI] [PubMed] [Google Scholar]
- 25.Hess B, Kutzner C, van der Spoel D, Lindahl E. 2008. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435–447. doi: 10.1021/ct700301q. [DOI] [PubMed] [Google Scholar]
- 26.Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, Shirts MR, Smith JC, Kasson PM, van der Spoel D, Hess B, Lindahl E. 2013. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29:845–854. doi: 10.1093/bioinformatics/btt055. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All PDB structure files can be found on the download page at the website for the Center of Excellence for African Swine Fever Genomics (https://asfvgenomics.com/) or in ModelArchive at https://modelarchive.org/doi/10.5452/ma-asfv-asfvg. Individual ASFV protein structural predictions can also be found in Table 1.
TABLE 1.
Predicted structures of the 193 proteins encoded by ASFV strain Georgia 2007