11zw

Structure of the Porcine deltacoronavirus (PDCoV) receptor-binding domain bound to the RBD minibinder 11, the PD3 Fab, and the Kappa light chain nanobody

spinqualitylabelsall models 11zw, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 11zw is a 5 chain structure with sequence from Lama glama, Mus musculus, Porcine deltacoronavirus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.8Å Ligands: BMA, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function W8Q9Y7_9NIDO PTPRS_CHICK Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycans (PubMed:11865065, PubMed:17178832). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth (By similarity). Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection (PubMed:17967490). Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as tyrosine phosphatase (PubMed:17967490). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (PubMed:17967490). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases. Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (By similarity).[UniProtKB:B0V2N1] Publication Abstract from PubMed Multiple spillovers of porcine deltacoronavirus (PDCoV) into humans in Haiti highlight its zoonotic potential and the need for targeted interventions. No approved vaccines or therapeutics are available for use in humans against any DCoVs. Here, we report the de novo design of PDCoV miniprotein inhibitors (aka minibinders, MBs) and show that one of them, MB11, binds with picomolar affinity to the PDCoV receptor-binding domain (RBD). MB11 potently inhibits PDCoV, outcompeting monoclonal antibodies, and cross-reacts with and broadly neutralizes a panel of distantly related DCoVs. We determined a cryoelectron microscopy structure of MB11 bound to the PDCoV RBD which reveals the molecular basis of broad DCoV neutralization through interference with host receptor engagement. Deep mutational scanning of the PDCoV RBD reveals that MB11 has a high barrier to viral escape with only few mutations mediating escape without dampening APN receptor binding. MB11 resists stringent biochemical stresses, including high temperature, low pH, and proteolysis, which may enable delivery to various tissues for viral inhibition. This work delineates a prime candidate for clinical evaluation against PDCoV infection and for pandemic preparedness. Computational design of an ultrapotent deltacoronavirus miniprotein inhibitor.,Avery NG, Yoshiyama CN, Taylor AL, Park YJ, Asarnow D, Perruzza L, Brown JT, Corti D, Benigni F, Starr TN, Veesler D Proc Natl Acad Sci U S A. 2026 May 5;123(18):e2533456123. doi: , 10.1073/pnas.2533456123. Epub 2026 Apr 29. PMID:42054371 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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