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==== | ==Structure of Human Parainfluenza Virus 3 Unassembled Nucleoprotein in Complex with its viral chaperone== | ||
<StructureSection load='7ev8' size='340' side='right'caption='[[7ev8]]' scene=''> | <StructureSection load='7ev8' size='340' side='right'caption='[[7ev8]], [[Resolution|resolution]] 3.23Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ev8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_parainfluenza_3_virus_(strain_NIH_47885) Human parainfluenza 3 virus (strain NIH 47885)] and [https://en.wikipedia.org/wiki/Human_respirovirus_3 Human respirovirus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EV8 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=7ev8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ev8 OCA], [https://pdbe.org/7ev8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ev8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ev8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ev8 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.234Å</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=7ev8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ev8 OCA], [https://pdbe.org/7ev8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ev8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ev8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ev8 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/PHOSP_PI3H4 PHOSP_PI3H4] Essential component of the RNA polymerase and the nascent chain assembly complex. Also required during RNA synthesis. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human parainfluenza virus 3 (HPIV3) belongs to the Paramyxoviridae, causing annual worldwide epidemics of respiratory diseases, especially in newborns and infants. The core components consist of just three viral proteins: nucleoprotein (N), phosphoprotein (P), and RNA polymerase (L), playing essential roles in replication and transcription of HPIV3 as well as other paramyxoviruses. Viral genome encapsidated by N is as a template and recognized by RNA-dependent RNA polymerase complex composed of L and P. The offspring RNA also needs to assemble with N to form nucleocapsids. The N is one of the most abundant viral proteins in infected cells and chaperoned in the RNA-free form (N(0)) by P before encapsidation. In this study, we presented the structure of unassembled HPIV3 N(0) in complex with the N-terminal portion of the P, revealing the molecular details of the N(0) and the conserved N(0)-P interaction. Combined with biological experiments, we showed that the P binds to the C-terminal domain of N(0) mainly by hydrophobic interaction and maintains the unassembled conformation of N by interfering with the formation of N-RNA oligomers, which might be a target for drug development. Based on the complex structure, we developed a method to obtain the monomeric N(0). Furthermore, we designed a P-derived fusion peptide with 10-fold higher affinity, which hijacked the N and interfered with the binding of the N to RNA significantly. Finally, we proposed a model of conformational transition of N from the unassembled state to the assembled state, which helped to further understand viral replication. IMPORTANCE Human parainfluenza virus 3 (HPIV3) causes annual epidemics of respiratory diseases, especially in newborns and infants. For the replication of HPIV3 and other paramyxoviruses, only three viral proteins are required: phosphoprotein (P), RNA polymerase (L), and nucleoprotein (N). Here, we report the crystal structure of the complex of N and its chaperone P. We describe in detail how P acts as a chaperone to maintain the unassembled conformation of N. Our analysis indicated that the interaction between P and N is conserved and mediated by hydrophobicity, which can be used as a target for drug development. We obtained a high-affinity P-derived peptide inhibitor, specifically targeted N, and greatly interfered with the binding of the N to RNA, thereby inhibiting viral encapsidation and replication. In summary, our results provide new insights into the paramyxovirus genome replication and nucleocapsid assembly and lay the basis for drug development. | |||
Structural Basis of Human Parainfluenza Virus 3 Unassembled Nucleoprotein in Complex with Its Viral Chaperone.,Dong X, Wang X, Xie M, Wu W, Chen Z J Virol. 2022 Jan 26;96(2):e0164821. doi: 10.1128/JVI.01648-21. Epub 2021 Nov 3. PMID:34730394<ref>PMID:34730394</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ev8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human respirovirus 3]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Z | [[Category: Chen Z]] | ||
[[Category: Dong XF]] | |||