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6pzk

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Revision as of 04:45, 11 April 2020

Cryo-EM Structure of the Respiratory Syncytial Virus Polymerase (L) Protein Bound by the Tetrameric Phosphoprotein (P)

6pzk, resolution 3.20Å

Structural highlights

6pzk is a 5 chain structure with sequence from Hrsva. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[L_HRSVA] Displays RNA-directed RNA polymerase, mRNA guanylyl transferase, mRNA (guanine-N(7)-)-methyltransferase and poly(A) synthetase activities. The viral mRNA guanylyl transferase displays a different biochemical reaction than the cellular enzyme. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). Functions either as transcriptase or as replicase. The transcriptase synthesizes subsequently the subgenomic RNAs, assuring their capping and polyadenylation by a stuttering mechanism. The replicase mode is dependent on intracellular protein N concentration. In this mode, the polymerase replicates the whole viral genome without recognizing the transcriptional signals (By similarity).^[1] [PHOSP_HRSVA] Acts as a cofactor that serves both to stabilize the protein L and to place the polymerase complex on the N:RNA template.

Publication Abstract from PubMed

Numerous interventions are in clinical development for respiratory syncytial virus (RSV) infection, including small molecules that target viral transcription and replication. These processes are catalyzed by a complex comprising the RNA-dependent RNA polymerase (L) and the tetrameric phosphoprotein (P). RSV P recruits multiple proteins to the polymerase complex and, with the exception of its oligomerization domain, is thought to be intrinsically disordered. Despite their critical roles in RSV transcription and replication, structures of L and P have remained elusive. Here, we describe the 3.2-A cryo-EM structure of RSV L bound to tetrameric P. The structure reveals a striking tentacular arrangement of P, with each of the four monomers adopting a distinct conformation. The structure also rationalizes inhibitor escape mutants and mutations observed in live-attenuated vaccine candidates. These results provide a framework for determining the molecular underpinnings of RSV replication and transcription and should facilitate the design of effective RSV inhibitors.

Structure of the Respiratory Syncytial Virus Polymerase Complex.,Gilman MSA, Liu C, Fung A, Behera I, Jordan P, Rigaux P, Ysebaert N, Tcherniuk S, Sourimant J, Eleouet JF, Sutto-Ortiz P, Decroly E, Roymans D, Jin Z, McLellan JS Cell. 2019 Sep 19;179(1):193-204.e14. doi: 10.1016/j.cell.2019.08.014. Epub 2019 , Sep 5. PMID:31495574^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Barik S. The structure of the 5' terminal cap of the respiratory syncytial virus mRNA. J Gen Virol. 1993 Mar;74 ( Pt 3):485-90. PMID:8445369
↑ Gilman MSA, Liu C, Fung A, Behera I, Jordan P, Rigaux P, Ysebaert N, Tcherniuk S, Sourimant J, Eleouet JF, Sutto-Ortiz P, Decroly E, Roymans D, Jin Z, McLellan JS. Structure of the Respiratory Syncytial Virus Polymerase Complex. Cell. 2019 Sep 19;179(1):193-204.e14. doi: 10.1016/j.cell.2019.08.014. Epub 2019 , Sep 5. PMID:31495574 doi:http://dx.doi.org/10.1016/j.cell.2019.08.014

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6pzk"

@@ Line 3: / Line 3: @@
 <SX load='6pzk' size='340' side='right' viewer='molstar' caption='[[6pzk]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6pzk]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsva Hrsva]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PZK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PZK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6pzk]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsva Hrsva]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PZK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PZK FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6pzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pzk OCA], [http://pdbe.org/6pzk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pzk RCSB], [http://www.ebi.ac.uk/pdbsum/6pzk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pzk ProSAT]</span></td></tr>
+</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=6pzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pzk OCA], [http://pdbe.org/6pzk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pzk RCSB], [http://www.ebi.ac.uk/pdbsum/6pzk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pzk ProSAT]</span></td></tr>
 </table>
 == Function ==

6pzk

From Proteopedia

Revision as of 04:45, 11 April 2020

Cryo-EM Structure of the Respiratory Syncytial Virus Polymerase (L) Protein Bound by the Tetrameric Phosphoprotein (P)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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