5w5m | pdb_00005w5m

Crystal structure of human IgG4-Sigma1 Fc fragment

spinqualitylabelsall models 5w5m, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5w5m is a 2 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 1.9Å Ligands: ACT, BMA, FUC, GAL, GOL, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IGHG4_HUMAN Publication Abstract from PubMed Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcgamma) receptor-expressing immune cells. We previously reported on a human IgG2 variant termed IgG2sigma with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and Fcgamma receptor binding assays. Here, we extend that work to IgG1 and IgG4 antibodies, alternative subtypes which may offer advantages over IgG2 antibodies. In several in vitro and in vivo assays, the IgG1sigma and IgG4sigma variants showed equal or even lower Fc-related activities than the corresponding IgG2sigma variant. In particular, IgG1sigma and IgG4sigma variants demonstrate complete lack of effector function as measured by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and in vivo T-cell activation. The IgG1sigma and IgG4sigma variants showed acceptable solubility and stability, and typical human IgG1 pharmacokinetic profiles in human FcRn-transgenic mice and cynomolgus monkeys. In silico T-cell epitope analyses predict a lack of immunogenicity in humans. Finally, crystal structures and simulations of the IgG1sigma and IgG4sigma Fc domains can explain the lack of Fc-mediated immune functions. These variants show promise for use in those therapeutic antibodies and Fc fusions for which the Fc domain should be immunologically "silent". Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality.,Tam SH, McCarthy SG, Armstrong AA, Somani S, Wu SJ, Liu X, Gervais A, Ernst R, Saro D, Decker R, Luo J, Gilliland GL, Chiu ML, Scallon BJ Antibodies (Basel). 2017 Sep 1;6(3). pii: antib6030012. doi:, 10.3390/antib6030012. PMID:31548527 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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