7kyl

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Powassan virus Envelope protein DIII in complex with neutralizing Fab POWV-80

Structural highlights

7kyl is a 6 chain structure with sequence from Deer tick virus and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:CL, NA, PCA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

E2I7G7_9FLAV Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504]

Publication Abstract from PubMed

Although Powassan virus (POWV) is an emerging tick-transmitted flavivirus that causes severe or fatal neuroinvasive disease in humans, medical countermeasures have not yet been developed. Here, we developed a panel of neutralizing anti-POWV mAbs recognizing six distinct antigenic sites. The most potent of these mAbs bind sites within domain II or III of the envelope (E) protein and inhibit postattachment viral entry steps. A subset of these mAbs cross-react with other flaviviruses. Both POWV type-specific and cross-reactive neutralizing mAbs confer protection in mice against POWV infection when given as prophylaxis or postexposure therapy. Several cross-reactive mAbs mapping to either domain II or III also protect in vivo against heterologous tick-transmitted flaviviruses including Langat and tick-borne encephalitis virus. Our experiments define structural and functional correlates of antibody protection against POWV infection and identify epitopes targeted by broadly neutralizing antibodies with therapeutic potential against multiple tick-borne flaviviruses.

Broadly neutralizing monoclonal antibodies protect against multiple tick-borne flaviviruses.,VanBlargan LA, Errico JM, Kafai NM, Burgomaster KE, Jethva PN, Broeckel RM, Meade-White K, Nelson CA, Himansu S, Wang D, Handley SA, Gross ML, Best SM, Pierson TC, Fremont DH, Diamond MS J Exp Med. 2021 May 3;218(5):e20210174. doi: 10.1084/jem.20210174. PMID:33831142[1]

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

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See Also

References

  1. VanBlargan LA, Errico JM, Kafai NM, Burgomaster KE, Jethva PN, Broeckel RM, Meade-White K, Nelson CA, Himansu S, Wang D, Handley SA, Gross ML, Best SM, Pierson TC, Fremont DH, Diamond MS. Broadly neutralizing monoclonal antibodies protect against multiple tick-borne flaviviruses. J Exp Med. 2021 May 3;218(5):e20210174. PMID:33831142 doi:10.1084/jem.20210174

Contents


PDB ID 7kyl

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