6wol | pdb_00006wol

Next generation monomeric IgG4 Fc bound to neonatal Fc receptor

spinqualitylabelsall models 6wol, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wol is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Ligands: BMA, FUL, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FCGRN_HUMAN Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus. Publication Abstract from PubMed In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life. In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.,Shan L, Dyk NV, Haskins N, Cook KM, Rosenthal KL, Mazor R, Dragulin-Otto S, Jiang Y, Wu H, Dall'Acqua WF, Borrok MJ, Damschroder MM, Oganesyan V Commun Biol. 2021 Sep 8;4(1):1048. doi: 10.1038/s42003-021-02565-5. PMID:34497355 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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