|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1l1n' size='340' side='right'caption='[[1l1n]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1l1n' size='340' side='right'caption='[[1l1n]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1l1n]] is a 2 chain structure with sequence from [http://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=1L1N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1L1N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1l1n]] 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=1L1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L1N FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12081 Human poliovirus 1 Mahoney])</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]] 2.1Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </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=1l1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l1n OCA], [https://pdbe.org/1l1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l1n RCSB], [https://www.ebi.ac.uk/pdbsum/1l1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l1n ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1l1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l1n OCA], [http://pdbe.org/1l1n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l1n RCSB], [http://www.ebi.ac.uk/pdbsum/1l1n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l1n ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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/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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 20: |
Line 19: |
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1l1n ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1l1n ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| - | <div style="background-color:#fffaf0;"> | |
| - | == Publication Abstract from PubMed == | |
| - | The X-ray crystallographic structure of the recombinant poliovirus 3C gene product (Mahoney strain) has been determined by single isomorphous replacement and non-crystallographic symmetry averaging and refined at 2.1 A resolution. Poliovirus 3C is comprised of two six-stranded antiparallel beta-barrel domains and is structurally similar to the chymotrypsin-like serine proteinases. The shallow active site cleft is located at the junction of the two beta-barrel domains and contains a His40, Glu71, Cys147 catalytic triad. The polypeptide loop preceding Cys147 is flexible and likely undergoes a conformational change upon substrate binding. The specificity pockets for poliovirus 3C are well-defined and modeling studies account for the known substrate specificity of this proteinase. Poliovirus 3C also participates in the formation of the viral replicative initiation complex where it specifically recognizes and binds the RNA stem-loop structure in the 5' non-translated region of its own genome. The RNA recognition site of 3C is located on the opposite side of the molecule in relation to its proteolytic active site and is centered about the conserved KFRDIR sequence of the domain linker. The recognition site is well-defined and also includes residues from the amino and carboxy-terminal helices. The two molecules in the asymmetric unit are related by an approximate 2-fold, non-crystallographic symmetry and form an intermolecular antiparallel beta-sheet at their interface. | |
| - | | |
| - | Refined X-ray crystallographic structure of the poliovirus 3C gene product.,Mosimann SC, Cherney MM, Sia S, Plotch S, James MN J Mol Biol. 1997 Nov 14;273(5):1032-47. PMID:9367789<ref>PMID:9367789</ref> | |
| - | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | </div> | |
| - | <div class="pdbe-citations 1l1n" style="background-color:#fffaf0;"></div> | |
| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[Proteinase 3D structures|Proteinase 3D structures]] |
| | *[[Tobacco Etch Virus (TEV) Protease|Tobacco Etch Virus (TEV) Protease]] | | *[[Tobacco Etch Virus (TEV) Protease|Tobacco Etch Virus (TEV) Protease]] |
| | *[[Virus protease 3D structures|Virus protease 3D structures]] | | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| Line 37: |
Line 28: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human poliovirus 1 mahoney]] | + | [[Category: Human poliovirus 1 Mahoney]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Picornain 3C]]
| + | [[Category: Chernaia MM]] |
| - | [[Category: Chernaia, M M]] | + | [[Category: James MNG]] |
| - | [[Category: James, M N.G]] | + | [[Category: Mosimann SC]] |
| - | [[Category: Mosimann, S C]] | + | [[Category: Plotch S]] |
| - | [[Category: Plotch, S]] | + | [[Category: Sia S]] |
| - | [[Category: Sia, S]] | + | |
| - | [[Category: Beta barrel]]
| + | |
| - | [[Category: Catalytic triad]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Trypsin-like]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
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
|
