3ro5

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Current revision (09:44, 1 March 2024) (edit) (undo)
 
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<StructureSection load='3ro5' size='340' side='right'caption='[[3ro5]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
<StructureSection load='3ro5' size='340' side='right'caption='[[3ro5]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3ro5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/I33a0 I33a0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RO5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3ro5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Wilson-Smith/1933(H1N1)) Influenza A virus (A/Wilson-Smith/1933(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RO5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LGH:[4-(2-CHLORO-4-NITROPHENYL)PIPERAZIN-1-YL][3-(2-METHOXYPHENYL)-5-METHYL-1,2-OXAZOL-4-YL]METHANONE'>LGH</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.66&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=381518 I33A0])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LGH:[4-(2-CHLORO-4-NITROPHENYL)PIPERAZIN-1-YL][3-(2-METHOXYPHENYL)-5-METHYL-1,2-OXAZOL-4-YL]METHANONE'>LGH</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=3ro5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ro5 OCA], [https://pdbe.org/3ro5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ro5 RCSB], [https://www.ebi.ac.uk/pdbsum/3ro5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ro5 ProSAT]</span></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=3ro5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ro5 OCA], [https://pdbe.org/3ro5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ro5 RCSB], [https://www.ebi.ac.uk/pdbsum/3ro5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ro5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/Q1K9H2_I33A0 Q1K9H2_I33A0]] Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals and is responsible of the active RNP import into the nucleus through the cellular importin alpha/beta pathway. Later in the infection, nucleus export of RNP are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that the nucleoprotein binds directly exportin-1 (XPO1) and plays an active role in RNP nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmask nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus (By similarity).[SAAS:SAAS002141_004_603280]
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[https://www.uniprot.org/uniprot/Q1K9H2_I33A0 Q1K9H2_I33A0] Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals and is responsible of the active RNP import into the nucleus through the cellular importin alpha/beta pathway. Later in the infection, nucleus export of RNP are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that the nucleoprotein binds directly exportin-1 (XPO1) and plays an active role in RNP nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmask nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus (By similarity).[SAAS:SAAS002141_004_603280]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target for antiviral intervention, and inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered a structurally similar series of influenza replication inhibitors and show that they interfere with NP-dependent processes via formation of higher-order NP oligomers. Support for this unique mechanism is provided by site-directed mutagenesis studies, biophysical characterization of the oligomeric ligand:NP complex, and an X-ray cocrystal structure of an NP dimer of trimers (or hexamer) comprising three NP_A:NP_B dimeric subunits. Each NP_A:NP_B dimeric subunit contains two ligands that bridge two composite, protein-spanning binding sites in an antiparallel orientation to form a stable quaternary complex. Optimization of the initial screening hit produced an analog that protects mice from influenza-induced weight loss and mortality by reducing viral titers to undetectable levels throughout the course of treatment.
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Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers.,Gerritz SW, Cianci C, Kim S, Pearce BC, Deminie C, Discotto L, McAuliffe B, Minassian BF, Shi S, Zhu S, Zhai W, Pendri A, Li G, Poss MA, Edavettal S, McDonnell PA, Lewis HA, Maskos K, Mortl M, Kiefersauer R, Steinbacher S, Baldwin ET, Metzler W, Bryson J, Healy MD, Philip T, Zoeckler M, Schartman R, Sinz M, Leyva-Grado VH, Hoffmann HH, Langley DR, Meanwell NA, Krystal M Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15366-71. Epub 2011 Sep 6. PMID:21896751<ref>PMID:21896751</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3ro5" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: I33a0]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Baldwin, E T]]
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[[Category: Baldwin ET]]
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[[Category: Edavettal, S]]
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[[Category: Edavettal S]]
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[[Category: Kiefersauer, R]]
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[[Category: Kiefersauer R]]
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[[Category: Langley, D R]]
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[[Category: Langley DR]]
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[[Category: Lewis, H A]]
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[[Category: Lewis HA]]
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[[Category: Maskos, K]]
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[[Category: Maskos K]]
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[[Category: McDonnell, P A]]
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[[Category: McDonnell PA]]
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[[Category: Mortl, M]]
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[[Category: Mortl M]]
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[[Category: Pearce, B C]]
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[[Category: Pearce BC]]
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[[Category: Steinbacher, S]]
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[[Category: Steinbacher S]]
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[[Category: Influenza nucleoprotein]]
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[[Category: Viral protein]]
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Current revision

Crystal structure of influenza A virus nucleoprotein with ligand

PDB ID 3ro5

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