View source for 6klc


==Structure of apo Lassa virus polymerase==
<StructureSection load='6klc' size='340' side='right'caption='[[6klc]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6klc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lassa_mammarenavirus Lassa mammarenavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KLC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KLC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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=6klc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6klc OCA], [http://pdbe.org/6klc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6klc RCSB], [http://www.ebi.ac.uk/pdbsum/6klc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6klc ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/A0A097F4L1_9VIRU A0A097F4L1_9VIRU]] 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.[HAMAP-Rule:MF_04086][PIRNR:PIRNR000836] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health(1-4). These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome(5). Viral polymerases are one of the leading antiviral therapeutic targets. However, the structure of arenavirus polymerase is not yet known. Here we report the near-atomic resolution structures of Lassa and Machupo virus polymerases in both apo and promoter-bound forms. These structures display a similar overall architecture to influenza virus and bunyavirus polymerases but possess unique local features, including an arenavirus-specific insertion domain that regulates the polymerase activity. Notably, the ordered active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5'-viral RNA, which is a necessity for both influenza virus and bunyavirus polymerases(6,7). Moreover, dimerization could facilitate the polymerase activity. These findings advance our understanding of the mechanism of arenavirus replication and provide an important basis for developing antiviral therapeutics.

Structural insight into arenavirus replication machinery.,Peng R, Xu X, Jing J, Wang M, Peng Q, Liu S, Wu Y, Bao X, Wang P, Qi J, Gao GF, Shi Y Nature. 2020 Mar;579(7800):615-619. doi: 10.1038/s41586-020-2114-2. Epub 2020 Mar, 18. PMID:32214249<ref>PMID:32214249</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6klc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lassa mammarenavirus]]
[[Category: Gao, G F]]
[[Category: Jing, J]]
[[Category: Peng, Q]]
[[Category: Peng, R]]
[[Category: Shi, Y]]
[[Category: Xu, X]]
[[Category: Polymerase]]
[[Category: Rna virus]]
[[Category: Viral protein]]