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| | <StructureSection load='5b7b' size='340' side='right'caption='[[5b7b]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='5b7b' size='340' side='right'caption='[[5b7b]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5b7b]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/I33a0 I33a0]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4x9a 4x9a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B7B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5b7b]] is a 6 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))]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4x9a 4x9a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B7B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NUZ:[4-(2-CHLORO-4-NITROPHENYL)PIPERAZIN-1-YL](5-METHYL-3-PHENYL-1,2-OXAZOL-4-YL)METHANONE'>NUZ</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NUZ:[4-(2-CHLORO-4-NITROPHENYL)PIPERAZIN-1-YL](5-METHYL-3-PHENYL-1,2-OXAZOL-4-YL)METHANONE'>NUZ</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=381518 I33A0])</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=5b7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b7b OCA], [https://pdbe.org/5b7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b7b RCSB], [https://www.ebi.ac.uk/pdbsum/5b7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b7b ProSAT]</span></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=5b7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b7b OCA], [http://pdbe.org/5b7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b7b RCSB], [http://www.ebi.ac.uk/pdbsum/5b7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b7b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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] | + | [https://www.uniprot.org/uniprot/NCAP_I33A0 NCAP_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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: I33a0]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hao, Q]] | + | [[Category: Hao Q]] |
| - | [[Category: Pang, B]] | + | [[Category: Pang B]] |
| - | [[Category: Zhang, H M]] | + | [[Category: Zhang HM]] |
| - | [[Category: Zhang, W Z]] | + | [[Category: Zhang WZ]] |
| - | [[Category: Influenza nucleoprotein]]
| + | |
| - | [[Category: Nucleozin]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
NCAP_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).
Publication Abstract from PubMed
Influenza viruses are among the most common pathogens that threaten the health of humans and animals worldwide. Various anti-viral therapeutic agents are currently used for treatment and prophylaxis of influenza virus, but the targets of these drugs are easily mutated and result in resistance. Therefore, medications that have broad spectrum coverage are urgently needed to combat with the disease. Since nucleoprotein is regarded as a druggable target due to its conserved sequence and important functions during influenza virus life cycle, numerous studies are focused on this protein in attempts to develop broad-spectrum anti-influenza therapeutics. Recently, a novel small molecule compound, nucleozin, was found to induce large aggregates of nucleoprotein, which in turn caused cessation of virus replication. However, the aggregation-inducing mechanism of nucleozin has not been unveiled. Here we report the crystal structure of nucleoprotein-nucleozin complex at 3 A resolution, which shows the binding sites of nucleozin at nucleoprotein for the first time. The complex structure reveals how nucleoprotein and nucleozin interact with each other and hence result in nucleoprotein aggregates. The structural information is envisaged to help accelerate the development of anti-influenza therapeutic agents.
Structural Characterization of H1N1 Nucleoprotein-Nucleozin Binding Sites.,Pang B, Cheung NN, Zhang W, Dai J, Kao RY, Zhang H, Hao Q Sci Rep. 2016 Jul 11;6:29684. doi: 10.1038/srep29684. PMID:27404920[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pang B, Cheung NN, Zhang W, Dai J, Kao RY, Zhang H, Hao Q. Structural Characterization of H1N1 Nucleoprotein-Nucleozin Binding Sites. Sci Rep. 2016 Jul 11;6:29684. doi: 10.1038/srep29684. PMID:27404920 doi:http://dx.doi.org/10.1038/srep29684
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