View source for 7ojn


==Lassa virus L protein in an elongation conformation [ELONGATION]==
<StructureSection load='7ojn' size='340' side='right'caption='[[7ojn]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ojn]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mammarenavirus_lassaense Mammarenavirus lassaense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJN 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]] 2.92&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KH:5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]URIDINE'>2KH</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=7ojn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ojn OCA], [https://pdbe.org/7ojn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ojn RCSB], [https://www.ebi.ac.uk/pdbsum/7ojn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ojn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A3S8NV63_LASV A0A3S8NV63_LASV] RNA-dependent RNA polymerase, which is responsible for the replication and transcription of the viral RNA genome using antigenomic RNA as an intermediate. During transcription, synthesizes subgenomic RNAs and assures their capping by a cap-snatching mechanism, which involves the endonuclease activity cleaving the host capped pre-mRNAs. These short capped RNAs are then used as 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]
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== Publication Abstract from PubMed ==
Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we present nine cryo-EM structures of the L protein in the apo-, promoter-bound pre-initiation and active RNA synthesis states. We characterize distinct binding pockets for the conserved 3' and 5' promoter RNAs and show how full-promoter binding induces a distinct pre-initiation conformation. In the apo- and early elongation states, the endonuclease is inhibited by two distinct L protein peptides, whereas in the pre-initiation state it is uninhibited. In the early elongation state, a template-product duplex is bound in the active site cavity together with an incoming non-hydrolysable nucleotide and the full C-terminal region of the L protein, including the putative cap-binding domain, is well-ordered. These data advance our mechanistic understanding of how this flexible and multifunctional molecular machine is activated.

Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity.,Kouba T, Vogel D, Thorkelsson SR, Quemin ERJ, Williams HM, Milewski M, Busch C, Gunther S, Grunewald K, Rosenthal M, Cusack S Nat Commun. 2021 Dec 2;12(1):7018. doi: 10.1038/s41467-021-27305-5. PMID:34857749<ref>PMID:34857749</ref>

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

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mammarenavirus lassaense]]
[[Category: Busch C]]
[[Category: Cusack S]]
[[Category: Grunewald K]]
[[Category: Gunther S]]
[[Category: Kouba T]]
[[Category: Milewski M]]
[[Category: Quemin E]]
[[Category: Rosenthal M]]
[[Category: Thorkelsson S]]
[[Category: Vogel D]]
[[Category: Williams HM]]