|
|
| Line 4: |
Line 4: |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[8fm9]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Flock_House_virus Flock House virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FM9 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[8fm9]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Flock_House_virus Flock House virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FM9 FirstGlance]. <br> |
| - | </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=8fm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fm9 OCA], [https://pdbe.org/8fm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fm9 RCSB], [https://www.ebi.ac.uk/pdbsum/8fm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fm9 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</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=8fm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fm9 OCA], [https://pdbe.org/8fm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fm9 RCSB], [https://www.ebi.ac.uk/pdbsum/8fm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fm9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [https://www.uniprot.org/uniprot/RDRP_FHV RDRP_FHV] RNA-dependent RNA polymerase which replicates the viral genome composed of 2 RNA segments, RNA1 and RNA2. | + | [https://www.uniprot.org/uniprot/RDRP_FHV RDRP_FHV] RNA-dependent RNA polymerase, which replicates the viral genome composed of 2 RNA segments, RNA1 and RNA2 (Probable). Does not need an exogenous primer (PubMed:24466277). Also possesses a terminal nucleotidyl transferase (TNTase) activity (PubMed:24466277). The TNTase catalyzes the addition of nucleotide to the 3'-end of plus- and minus-stranded RNAs, probably to repair the 3'-end nucleotide loss (PubMed:24466277). Forms the open necked connection to the cytosol of the virus-induced replication vesicles (PubMed:32690711, PubMed:36560715, PubMed:36693094). Mediates viral RNA1 recruitment (PubMed:17301137).<ref>PMID:17301137</ref> <ref>PMID:24466277</ref> <ref>PMID:32690711</ref> <ref>PMID:36560715</ref> <ref>PMID:36693094</ref> <ref>PMID:24466277</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Positive-strand RNA viruses replicate their genomes in virus-induced membrane vesicles, and the resulting RNA replication complexes are a major target for virus control. Nodavirus studies first revealed viral RNA replication proteins forming a 12-fold symmetric "crown" at the vesicle opening to the cytosol, an arrangement recently confirmed to extend to distantly related alphaviruses. Using cryoelectron microscopy (cryo-EM), we show that mature nodavirus crowns comprise two stacked 12-mer rings of multidomain viral RNA replication protein A. Each ring contains an ~19 nm circle of C-proximal polymerase domains, differentiated by strikingly diverged positions of N-proximal RNA capping/membrane binding domains. The lower ring is a "proto-crown" precursor that assembles prior to RNA template recruitment, RNA synthesis, and replication vesicle formation. In this proto-crown, the N-proximal segments interact to form a toroidal central floor, whose 3.1 A resolution structure reveals many mechanistic details of the RNA capping/membrane binding domains. In the upper ring, cryo-EM fitting indicates that the N-proximal domains extend radially outside the polymerases, forming separated, membrane-binding "legs." The polymerase and N-proximal domains are connected by a long linker accommodating the conformational switch between the two rings and possibly also polymerase movements associated with RNA synthesis and nonsymmetric electron density in the lower center of mature crowns. The results reveal remarkable viral protein multifunctionality, conformational flexibility, and evolutionary plasticity and insights into (+)RNA virus replication and control.
| + | |
| | | | |
| - | Nodavirus RNA replication crown architecture reveals proto-crown precursor and viral protein A conformational switching.,Zhan H, Unchwaniwala N, Rebolledo-Viveros A, Pennington J, Horswill M, Broadberry R, Myers J, den Boon JA, Grant T, Ahlquist P Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2217412120. doi: , 10.1073/pnas.2217412120. Epub 2023 Jan 24. PMID:36693094<ref>PMID:36693094</ref>
| + | ==See Also== |
| - | | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 8fm9" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Function
RDRP_FHV RNA-dependent RNA polymerase, which replicates the viral genome composed of 2 RNA segments, RNA1 and RNA2 (Probable). Does not need an exogenous primer (PubMed:24466277). Also possesses a terminal nucleotidyl transferase (TNTase) activity (PubMed:24466277). The TNTase catalyzes the addition of nucleotide to the 3'-end of plus- and minus-stranded RNAs, probably to repair the 3'-end nucleotide loss (PubMed:24466277). Forms the open necked connection to the cytosol of the virus-induced replication vesicles (PubMed:32690711, PubMed:36560715, PubMed:36693094). Mediates viral RNA1 recruitment (PubMed:17301137).[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Van Wynsberghe PM, Chen HR, Ahlquist P. Nodavirus RNA replication protein a induces membrane association of genomic RNA. J Virol. 2007 May;81(9):4633-44. PMID:17301137 doi:10.1128/JVI.02267-06
- ↑ Wu W, Wang Z, Xia H, Liu Y, Qiu Y, Liu Y, Hu Y, Zhou X. Flock house virus RNA polymerase initiates RNA synthesis de novo and possesses a terminal nucleotidyl transferase activity. PLoS One. 2014 Jan 23;9(1):e86876. PMID:24466277 doi:10.1371/journal.pone.0086876
- ↑ Unchwaniwala N, Zhan H, Pennington J, Horswill M, den Boon JA, Ahlquist P. Subdomain cryo-EM structure of nodaviral replication protein A crown complex provides mechanistic insights into RNA genome replication. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18680-18691. PMID:32690711 doi:10.1073/pnas.2006165117
- ↑ den Boon JA, Zhan H, Unchwaniwala N, Horswill M, Slavik K, Pennington J, Navine A, Ahlquist P. Multifunctional Protein A Is the Only Viral Protein Required for Nodavirus RNA Replication Crown Formation. Viruses. 2022 Dec 3;14(12):2711. PMID:36560715 doi:10.3390/v14122711
- ↑ Zhan H, Unchwaniwala N, Rebolledo-Viveros A, Pennington J, Horswill M, Broadberry R, Myers J, den Boon JA, Grant T, Ahlquist P. Nodavirus RNA replication crown architecture reveals proto-crown precursor and viral protein A conformational switching. Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2217412120. doi: , 10.1073/pnas.2217412120. Epub 2023 Jan 24. PMID:36693094 doi:http://dx.doi.org/10.1073/pnas.2217412120
- ↑ Wu W, Wang Z, Xia H, Liu Y, Qiu Y, Liu Y, Hu Y, Zhou X. Flock house virus RNA polymerase initiates RNA synthesis de novo and possesses a terminal nucleotidyl transferase activity. PLoS One. 2014 Jan 23;9(1):e86876. PMID:24466277 doi:10.1371/journal.pone.0086876
|
