5TJW

Influenza A virus Nucleoprotein in Complex with Inhibitory Nanobody

Summary for 5TJW

• Entry DOI: 10.2210/pdb5tjw/pdb
• Descriptor: Nucleoprotein, NP-specific inhibitory VHH (2 entities in total)
• Functional Keywords: influenza, nucleoprotein, vhh, inhibitory, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/WSN/1933(H1N1)); More
• Total number of polymer chains: 2
• Total formula weight: 72517.20

Authors

Hanke, L.,Knockenhauer, K.E.,Ploegh, H.L.,Schwartz, T.U. (deposition date: 2016-10-05, release date: 2016-12-21, Last modification date: 2024-10-16)

Primary citation

Hanke, L.,Knockenhauer, K.E.,Brewer, R.C.,van Diest, E.,Schmidt, F.I.,Schwartz, T.U.,Ploegh, H.L.
The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment.
MBio, 7:-, 2016

PubMed Abstract: 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, αNP-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-Å crystal structure of αNP-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/αNP-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.

PubMed: 27965447
DOI: 10.1128/mBio.01569-16

Experimental method

X-RAY DIFFRACTION (3.231 Å)