View source for 7vgq


==Cryo-EM structure of Machupo virus polymerase L in complex with matrix protein Z==
<StructureSection load='7vgq' size='340' side='right'caption='[[7vgq]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vgq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Mammarenavirus_machupoense Mammarenavirus machupoense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VGQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7vgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vgq OCA], [https://pdbe.org/7vgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vgq RCSB], [https://www.ebi.ac.uk/pdbsum/7vgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vgq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/L_MACHU L_MACHU] RNA-dependent RNA polymerase which is responsible for replication and transcription of the viral RNA genome. During transcription, synthesizes 4 subgenomic RNAs, and assures their capping by a cap-snatching mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are heterogeneous and not polyadenylated. The replicase function is to direct synthesis of antigenomic and genomic RNA which are encapsidated and non capped. As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated. These processes may be regulated by proteins N and Z in a dose-dependent manner.
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== Publication Abstract from PubMed ==
The Arenaviridae family includes several viruses that cause severe human hemorrhagic fevers with high mortality, with no effective countermeasures currently available. The arenavirus multi-domain L protein is involved in viral transcription and replication and represents a promising target for antiviral drugs. The arenavirus matrix protein Z is a small multi-functional protein that inhibits the activities of the L protein. Here we report the structure of Machupo virus L protein in complex with Z determined by cryo-electron microscopy. The Z protein acts as a staple and binds the L protein with 1:1 stoichiometry at the intersection between the PA-C-like region, RNA-dependent RNA polymerase and PB2-N-like region. Binding of the Z protein may lock the multiple domains of L into a fixed arrangement leading to loss of catalytic activity. These results further our understanding of the inhibitory mechanism of arenavirus replication machinery and provide a novel perspective to develop antiviral drugs.

Structure of Machupo virus polymerase in complex with matrix protein Z.,Ma J, Zhang S, Zhang X Nat Commun. 2021 Oct 25;12(1):6163. doi: 10.1038/s41467-021-26432-3. PMID:34697302<ref>PMID:34697302</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7vgq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]]
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Mammarenavirus machupoense]]
[[Category: Ma J]]
[[Category: Zhang S]]
[[Category: Zhang X]]