This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5tjw

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 12:12, 23 September 2020

Influenza A virus Nucleoprotein in Complex with Inhibitory Nanobody

Structural highlights

5tjw is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B4URF1_9INFA] 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.[SAAS:SAAS00107710]

Publication Abstract from PubMed

Alpaca-derived single-domain antibody fragments (VHHs) that target the influenza A virus nucleoprotein (NP) can protect cells from infection when expressed in the cytosol. We found that one such VHH, alphaNP-VHH1, exhibits antiviral activity similar to that of Mx proteins by blocking nuclear import of incoming viral ribonucleoproteins (vRNPs) and viral transcription and replication in the nucleus. We determined a 3.2-A crystal structure of alphaNP-VHH1 in complex with influenza A virus NP. The VHH binds to a nonconserved region on the body domain of NP, which has been associated with binding to host factors and serves as a determinant of host range. Several of the NP/VHH interface residues determine sensitivity of NP to antiviral Mx GTPases. The structure of the NP/alphaNP-VHH1 complex affords a plausible explanation for the inhibitory properties of the VHH and suggests a rationale for the antiviral properties of Mx proteins. Such knowledge can be leveraged for much-needed novel antiviral strategies. IMPORTANCE: Influenza virus strains can rapidly escape from protection afforded by seasonal vaccines or acquire resistance to available drugs. Additional ways to interfere with the virus life cycle are therefore urgently needed. The influenza virus nucleoprotein is one promising target for antiviral interventions. We have previously isolated alpaca-derived single-domain antibody fragments (VHHs) that protect cells from influenza virus infection if expressed intracellularly. We show here that one such VHH exhibits antiviral activities similar to those of proteins of the cellular antiviral defense (Mx proteins). We determined the three-dimensional structure of this VHH in complex with the influenza virus nucleoprotein and identified the interaction site, which overlaps regions that determine sensitivity of the virus to Mx proteins. Our data define a new vulnerability of influenza virus, help us to better understand the cellular antiviral mechanisms, and provide a well-characterized tool to further study them.

The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment.,Hanke L, Knockenhauer KE, Brewer RC, van Diest E, Schmidt FI, Schwartz TU, Ploegh HL MBio. 2016 Dec 13;7(6). pii: e01569-16. doi: 10.1128/mBio.01569-16. PMID:27965447^[1]

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

References

↑ Hanke L, Knockenhauer KE, Brewer RC, van Diest E, Schmidt FI, Schwartz TU, Ploegh HL. The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment. MBio. 2016 Dec 13;7(6). pii: e01569-16. doi: 10.1128/mBio.01569-16. PMID:27965447 doi:http://dx.doi.org/10.1128/mBio.01569-16

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/5tjw"

@@ Line 1: / Line 1: @@
 ==Influenza A virus Nucleoprotein in Complex with Inhibitory Nanobody==
-<StructureSection load='5tjw' size='340' side='right' caption='[[5tjw]], [[Resolution|resolution]] 3.23&Aring;' scene=''>
+<StructureSection load='5tjw' size='340' side='right'caption='[[5tjw]], [[Resolution|resolution]] 3.23&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tjw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TJW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TJW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tjw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TJW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TJW 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=5tjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tjw OCA], [http://pdbe.org/5tjw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tjw RCSB], [http://www.ebi.ac.uk/pdbsum/5tjw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tjw 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=5tjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tjw OCA], [http://pdbe.org/5tjw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tjw RCSB], [http://www.ebi.ac.uk/pdbsum/5tjw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tjw ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
 </div>
 <div class="pdbe-citations 5tjw" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Hanke, L]]
 [[Category: Knockenhauer, K E]]

5tjw

From Proteopedia

Revision as of 12:12, 23 September 2020

Influenza A virus Nucleoprotein in Complex with Inhibitory Nanobody

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox