9msp

Crystal structure of MPXV A35R in complex with neutralizing antibody EV35-7

spinqualitylabelsall models 9msp, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9msp is a 8 chain structure with sequence from Homo sapiens and Monkeypox virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.19Å Ligands: ACT, EDO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PG161_MONPV Forms a complex with OPG162 and OPG190 to coordinate the incorporation of OPG164 into wrapped enveloped virion (EV) membranes and, subsequently, the production of actin tails. Therefore plays an essential role in efficient cell-to-cell spread of viral particles.[UniProtKB:P68617] Publication Abstract from PubMed The 2022 mpox outbreak highlighted the serious threat of monkeypox virus (MPXV), yet effective treatments are lacking. From an mpox-convalescent individual, we identified three high-affinity human monoclonal antibodies (mAbs) (named EV35-2, EV35-6, and EV35-7) that target the A35 protein in MPXV. These antibodies block viral spread in vitro and protect mice against lethal MPXV and vaccinia virus infection via both Fc-dependent and independent mechanisms. Levels of serum antibodies targeting the same epitopes are increased in mpox-convalescent humans, and higher levels of these antibodies in the sera are linked to shorter symptom duration and no hospitalization. Systems-level multivariate analysis indicated that mpox-convalescent serum antibodies targeting the same epitopic region as these three mAbs may function cooperatively, with additive associations to clinical protection. Two of the antibodies use a conserved IGHD2-21-encoded CxGGDCx motif in their CDRH3 region to bind a highly conserved poxvirus epitope. These findings establish A35 as a critical therapeutic target and highlight A35-specific mAbs as promising candidates for next-generation orthopoxvirus treatments. Human monoclonal antibodies targeting A35 protect from death caused by mpox.,Fantin RF, Yuan M, Park SC, Bozarth B, Cohn H, Ignacio M, Earl P, Civljak A, Laghlali G, Zhang D, Zhu X, Crandell J, Monteiro V, Clark JJ, Cotter C, Burkhardt M, Singh G, Warang P, Garcia-Bernalt Diego J, Srivastava K, Lugo LA, Pischel L, Yildirim I, Omer SB, da Silva D, Krammer F, Bajic G, Simon V, Schotsaert M, Lucas C, Wilson IA, Moss B, Coelho CH Cell. 2025 Aug 26:S0092-8674(25)00918-3. doi: 10.1016/j.cell.2025.08.004. PMID:40865529 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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