| Structural highlights
Function
[POLG_POL1M] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The interaction of five VP1 proteins in the fivefold axes results in a prominent protusion extending to about 25 Angstroms from the capsid shell. The resulting structure appears as a steep plateau encircled by a valley or cleft. This depression also termed canyon is the receptor binding site. The capsid interacts with human PVR at this site to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis in Hela cells and through caveolin-mediated endocytosis in brain microvascular endothelial cells. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.[1] [2] [3] VP0 precursor is a component of immature procapsids (By similarity).[4] [5] [6] Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.[7] [8] [9] Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).[10] [11] [12] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities.[13] [14] [15] Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity).[16] [17] [18] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[19] [20] [21] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[22] [23] [24]
Publication Abstract from PubMed
Poliovirus (PV) 2CATPase is the most studied 2C protein in the Picornaviridae family. It is involved in RNA replication, encapsidation and uncoating and many inhibitors have been found that target PV 2CATPase. Despite numerous investigations to characterize its functions, a high-resolution structure of PV 2C has not yet been determined. We report here the crystal structure of a soluble fragment of PV 2CATPase to 2.55A, containing an ATPase domain, a zinc finger and a C-terminal helical domain but missing the N-terminal domain. The ATPase domain shares the common structural features with EV71 2C and other Superfamily 3 helicases. The C-terminal cysteine-rich motif folds into a CCCC type zinc finger in which four cysteine ligands and several auxiliary residues assist in zinc binding. By comparing with the known zinc finger fold groups, we found the zinc finger of 2C proteins belong to a new fold group, which we denote the "Enterovirus 2C-like" group. The C-terminus of PV 2CATPase forms an amphipathic helix that occupies a hydrophobic pocket located on an adjacent PV 2CATPase in the crystal lattice. The C-terminus mediated PV 2C-2C interaction promotes self-oligomerization, most likely hexamerization, which is fundamental to the ATPase activity of 2C. The zinc finger is the most structurally diverse feature in 2C proteins. Available structural and virological data suggest that the zinc finger of 2C might confer the specificity of interaction with other proteins. We built a hexameric ring model of PV 2CATPase and visualized the previously identified functional motifs and drug-resistant sites, thus providing a structure framework for antiviral drug development.
Crystal structure of a soluble fragment of poliovirus 2CATPase.,Guan H, Tian J, Zhang C, Qin B, Cui S PLoS Pathog. 2018 Sep 19;14(9):e1007304. doi: 10.1371/journal.ppat.1007304., eCollection 2018 Sep. PMID:30231078[25]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Ventoso I, MacMillan SE, Hershey JW, Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998 Sep 11;435(1):79-83. PMID:9755863
- ↑ Bubeck D, Filman DJ, Cheng N, Steven AC, Hogle JM, Belnap DM. The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. J Virol. 2005 Jun;79(12):7745-55. PMID:15919927 doi:79/12/7745
- ↑ Bergelson JM. New (fluorescent) light on poliovirus entry. Trends Microbiol. 2008 Feb;16(2):44-7. doi: 10.1016/j.tim.2007.12.004. Epub 2008 , Jan 10. PMID:18191571 doi:10.1016/j.tim.2007.12.004
- ↑ Guan H, Tian J, Zhang C, Qin B, Cui S. Crystal structure of a soluble fragment of poliovirus 2CATPase. PLoS Pathog. 2018 Sep 19;14(9):e1007304. doi: 10.1371/journal.ppat.1007304., eCollection 2018 Sep. PMID:30231078 doi:http://dx.doi.org/10.1371/journal.ppat.1007304
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