6j5d

Complex structure of MAb 4.2-scFv with louping ill virus envelope protein Domain III

spinqualitylabelsall models 6j5d, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6j5d is a 3 chain structure with sequence from Li and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: envelope (LI) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are members of the tick-borne flaviviruses (TBFVs) in the family Flaviviridae, which cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines against TBEV and LIV are available, infection rates are rising due to the low vaccination coverage. To date, no specific therapeutics have been licensed. Several neutralizing monoclonal antibodies (MAbs) show promising effectiveness in the control of TBFVs, but the underlying molecular mechanisms are yet to be characterized. Here, we determined the crystal structures of LIV envelope protein (E) and report the comparative structural analysis of a TBFV broadly neutralizing murine MAb (MAb 4.2) in complex with either LIV or TBEV E proteins. The structures reveal that MAb 4.2 binds to the lateral ridge of Domain III (EDIII) of LIV-E or TBEV-E, an epitope also reported for other potently neutralizing MAbs against mosquito-borne flaviviruses (MBFVs), but adopts a unique binding orientation. Further structural analysis suggested that MAb 4.2 may neutralize flavivirus infection by preventing the structural rearrangement required for membrane fusion during virus entry. These findings extend our understanding of the vulnerability of TBFVs and other flaviviruses (including MBFVs) and provide an avenue for antibody-based TBFVs antiviral development.ImportanceUnderstanding the mechanism of antibody neutralization/protection against a virus is crucial for antiviral counter-measures development. Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are tick-borne flaviviruses (TBFVs) in the family Flaviviridae They cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines for both viruses are available, infection rates are rising due to the low vaccination coverage. In this study, we solved the crystal structures of LIV envelope protein (E) and a broadly-neutralizing/protective TBFV MAb, MAb 4.2, in complex with E from either TBEV or LIV. Key structural features shared by TBFV E proteins were analyzed. Structures of E-antibody complexes show that MAb 4.2 targets the lateral ridge of both TBEV and LIV E proteins, a vulnerable site in flaviviruses for other potent neutralizing MAbs. Thus, this site represents a promising target for TBFV antiviral development. Further, these structures provide important information for understanding TBFV antigenicity. Molecular basis of a protective/neutralizing monoclonal antibody targeting envelope proteins of both tick-borne encephalitis virus and louping ill virus.,Yang X, Qi J, Peng R, Dai L, Gould EA, Gao GF, Tien P J Virol. 2019 Feb 13. pii: JVI.02132-18. doi: 10.1128/JVI.02132-18. PMID:30760569 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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