7zv1

Structural highlights

Function

POLG_AIVA8 Inhibits the integrated stress response (ISR) in the infected cell by preventing the sequestration of eIF2B by phosphorylated EIF2S1/eIF-2alpha (PubMed:32690955). Stress granule formation in response to EIF2S1/eIF-2alpha phosphorylation is thus inhibited, which allows protein synthesis and viral replication (PubMed:32690955). Does not have any proteolytic activity (PubMed:14512530). Required for viral RNA replication and viral RNA encapsidation (PubMed:14512530).^{[1] [2]} Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3 (PubMed:27595320, PubMed:27681122). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27595320, PubMed:27681122). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320).^{[3] [4]} Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3 (PubMed:27595320, PubMed:27681122). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27595320, PubMed:27681122). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320).^{[5] [6]} Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP1 (PubMed:27595320, PubMed:27681122). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27595320, PubMed:27681122). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320).^{[7] [8]} Required for viral RNA replication (PubMed:18653460). Does not have any proteolytic activity (PubMed:18653460).^[9] Affects membrane integrity and causes an increase in membrane permeability. Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.[UniProtKB:P03300] Serves as membrane anchor via its hydrophobic domain. Plays an essential role in viral RNA replication by recruiting PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (PubMed:22124328, PubMed:22258260, PubMed:24672044, PubMed:27989622, PubMed:30755512). Stimulates the enzymatic activity of PI4KB, this activation is sensitized by ACBD3 (PubMed:24672044, PubMed:27989622).^{[10] [11] [12] [13] [14]} Forms a primer, VPg-pU, which is utilized by the polymerase for the initiation of RNA chains.[UniProtKB:P03304] Cysteine protease that generates mature viral proteins from the precursor polyprotein (By similarity). In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate cooperatively bind to the protease (By similarity).[UniProtKB:P03304][UniProtKB:P12296] Replicates the genomic and antigenomic RNAs by recognizing replications specific signals (By similarity). Performs VPg uridylylation (By similarity).[UniProtKB:P12296]

References

1. ↑ Sasaki J, Nagashima S, Taniguchi K. Aichi virus leader protein is involved in viral RNA replication and encapsidation. J Virol. 2003 Oct;77(20):10799-807. PMID:14512530 doi:10.1128/jvi.77.20.10799-10807.2003
2. ↑ Rabouw HH, Visser LJ, Passchier TC, Langereis MA, Liu F, Giansanti P, van Vliet ALW, Dekker JG, van der Grein SG, Saucedo JG, Anand AA, Trellet ME, Bonvin AMJJ, Walter P, Heck AJR, de Groot RJ, van Kuppeveld FJM. Inhibition of the integrated stress response by viral proteins that block p-eIF2-eIF2B association. Nat Microbiol. 2020 Nov;5(11):1361-1373. PMID:32690955 doi:10.1038/s41564-020-0759-0
3. ↑ Zhu L, Wang X, Ren J, Kotecha A, Walter TS, Yuan S, Yamashita T, Tuthill TJ, Fry EE, Rao Z, Stuart DI. Structure of human Aichi virus and implications for receptor binding. Nat Microbiol. 2016 Sep 5;1:16150. doi: 10.1038/nmicrobiol.2016.150. PMID:27595320 doi:http://dx.doi.org/10.1038/nmicrobiol.2016.150
4. ↑ Sabin C, Fuzik T, Skubnik K, Palkova L, Lindberg AM, Plevka P. Structure of Aichi virus 1 and its empty particle: clues towards kobuvirus genome release mechanism. J Virol. 2016 Sep 28. pii: JVI.01601-16. PMID:27681122 doi:http://dx.doi.org/10.1128/JVI.01601-16
5. ↑ Zhu L, Wang X, Ren J, Kotecha A, Walter TS, Yuan S, Yamashita T, Tuthill TJ, Fry EE, Rao Z, Stuart DI. Structure of human Aichi virus and implications for receptor binding. Nat Microbiol. 2016 Sep 5;1:16150. doi: 10.1038/nmicrobiol.2016.150. PMID:27595320 doi:http://dx.doi.org/10.1038/nmicrobiol.2016.150
6. ↑ Sabin C, Fuzik T, Skubnik K, Palkova L, Lindberg AM, Plevka P. Structure of Aichi virus 1 and its empty particle: clues towards kobuvirus genome release mechanism. J Virol. 2016 Sep 28. pii: JVI.01601-16. PMID:27681122 doi:http://dx.doi.org/10.1128/JVI.01601-16
7. ↑ Zhu L, Wang X, Ren J, Kotecha A, Walter TS, Yuan S, Yamashita T, Tuthill TJ, Fry EE, Rao Z, Stuart DI. Structure of human Aichi virus and implications for receptor binding. Nat Microbiol. 2016 Sep 5;1:16150. doi: 10.1038/nmicrobiol.2016.150. PMID:27595320 doi:http://dx.doi.org/10.1038/nmicrobiol.2016.150
8. ↑ Sabin C, Fuzik T, Skubnik K, Palkova L, Lindberg AM, Plevka P. Structure of Aichi virus 1 and its empty particle: clues towards kobuvirus genome release mechanism. J Virol. 2016 Sep 28. pii: JVI.01601-16. PMID:27681122 doi:http://dx.doi.org/10.1128/JVI.01601-16
9. ↑ Sasaki J, Taniguchi K. Aichi virus 2A protein is involved in viral RNA replication. J Virol. 2008 Oct;82(19):9765-9. PMID:18653460 doi:10.1128/JVI.01051-08
10. ↑ Sasaki J, Ishikawa K, Arita M, Taniguchi K. ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites. EMBO J. 2012 Feb 1;31(3):754-66. PMID:22124328 doi:10.1038/emboj.2011.429
11. ↑ Greninger AL, Knudsen GM, Betegon M, Burlingame AL, Derisi JL. The 3A protein from multiple picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIβ. J Virol. 2012 Apr;86(7):3605-16. PMID:22258260 doi:10.1128/JVI.06778-11
12. ↑ Ishikawa-Sasaki K, Sasaki J, Taniguchi K. A complex comprising phosphatidylinositol 4-kinase IIIβ, ACBD3, and Aichi virus proteins enhances phosphatidylinositol 4-phosphate synthesis and is critical for formation of the viral replication complex. J Virol. 2014 Jun;88(12):6586-98. PMID:24672044 doi:10.1128/JVI.00208-14
13. ↑ McPhail JA, Ottosen EH, Jenkins ML, Burke JE. The Molecular Basis of Aichi Virus 3A Protein Activation of Phosphatidylinositol 4 Kinase IIIbeta, PI4KB, through ACBD3. Structure. 2016 Dec 7. pii: S0969-2126(16)30358-6. doi:, 10.1016/j.str.2016.11.016. PMID:27989622 doi:http://dx.doi.org/10.1016/j.str.2016.11.016
14. ↑ Lyoo H, van der Schaar HM, Dorobantu CM, Rabouw HH, Strating JRPM, van Kuppeveld FJM. ACBD3 Is an Essential Pan-enterovirus Host Factor That Mediates the Interaction between Viral 3A Protein and Cellular Protein PI4KB. mBio. 2019 Feb 12;10(1):e02742-18. PMID:30755512 doi:10.1128/mBio.02742-18