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| | <StructureSection load='2ijd' size='340' side='right'caption='[[2ijd]], [[Resolution|resolution]] 3.40Å' scene=''> | | <StructureSection load='2ijd' size='340' side='right'caption='[[2ijd]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ijd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_poliovirus_1_mahoney Human poliovirus 1 mahoney]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IJD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ijd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_poliovirus_1_Mahoney Human poliovirus 1 Mahoney]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IJD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3CD ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12081 Human poliovirus 1 Mahoney])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ijd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ijd OCA], [https://pdbe.org/2ijd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ijd RCSB], [https://www.ebi.ac.uk/pdbsum/2ijd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ijd ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ijd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ijd OCA], [https://pdbe.org/2ijd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ijd RCSB], [https://www.ebi.ac.uk/pdbsum/2ijd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ijd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/POLG_POL1M 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.<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> 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.<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities.<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> 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).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref> RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>
| + | [https://www.uniprot.org/uniprot/Q1PHW8_9ENTO Q1PHW8_9ENTO] Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[ARBA:ARBA00003366] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human poliovirus 1 mahoney]] | + | [[Category: Human poliovirus 1 Mahoney]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Filman, D J]] | + | [[Category: Filman DJ]] |
| - | [[Category: Gohara, D W]] | + | [[Category: Gohara DW]] |
| - | [[Category: Hogle, J M]] | + | [[Category: Hogle JM]] |
| - | [[Category: Marcotte, L L]] | + | [[Category: Marcotte LL]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Picornavirus]]
| + | |
| - | [[Category: Poliovirus]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Rna polymerase]]
| + | |
| - | [[Category: Rna-dependent rna polymerase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
Q1PHW8_9ENTO Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[ARBA:ARBA00003366]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Poliovirus 3CD is a multifunctional protein that serves as a precursor to the protease 3C(pro) and the viral polymerase 3D(pol) and also plays a role in the control of viral replication. Although 3CD is a fully functional protease, it lacks polymerase activity. We have solved the crystal structures of 3CD at a 3.4-A resolution and the G64S fidelity mutant of 3D(pol) at a 3.0-A resolution. In the 3CD structure, the 3C and 3D domains are joined by a poorly ordered polypeptide linker, possibly to facilitate its cleavage, in an arrangement that precludes intramolecular proteolysis. The polymerase active site is intact in both the 3CD and the 3D(pol) G64S structures, despite the disruption of a network proposed to position key residues in the active site. Therefore, changes in molecular flexibility may be responsible for the differences in fidelity and polymerase activities. Extensive packing contacts between symmetry-related 3CD molecules and the approach of the 3C domain's N terminus to the VPg binding site suggest how 3D(pol) makes biologically relevant interactions with the 3C, 3CD, and 3BCD proteins that control the uridylylation of VPg during the initiation of viral replication. Indeed, mutations designed to disrupt these interfaces have pronounced effects on the uridylylation reaction in vitro.
Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase.,Marcotte LL, Wass AB, Gohara DW, Pathak HB, Arnold JJ, Filman DJ, Cameron CE, Hogle JM J Virol. 2007 Apr;81(7):3583-96. Epub 2007 Jan 24. PMID:17251299[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Marcotte LL, Wass AB, Gohara DW, Pathak HB, Arnold JJ, Filman DJ, Cameron CE, Hogle JM. Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase. J Virol. 2007 Apr;81(7):3583-96. Epub 2007 Jan 24. PMID:17251299 doi:10.1128/JVI.02306-06
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