6vvu

Anti-Tryptase fab E104.v1 bound to tryptase

spinqualitylabelsall models 6vvu, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vvu is a 12 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 3Å Ligands: 0GJ, CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRYB1_HUMAN Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity). Publication Abstract from PubMed Human beta-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of allergic inflammatory responses in asthma. Antibodies generally inhibit proteases by blocking substrate access by binding to active sites or exosites or by allosteric modulation. The bivalency of IgG antibodies can increase potency via avidity, but has never been described as essential for activity. Here we report an inhibitory anti-tryptase IgG antibody with a bivalency-driven mechanism of action. Using biochemical and structural data, we determine that four Fabs simultaneously occupy four exosites on the beta-tryptase tetramer, inducing allosteric changes at the small interface. In the presence of heparin, the monovalent Fab shows essentially no inhibition, whereas the bivalent IgG fully inhibits beta-tryptase activity in a hinge-dependent manner. Our results suggest a model where the bivalent IgG acts akin to molecular pliers, pulling the tetramer apart into inactive beta-tryptase monomers, and may provide an alternative strategy for antibody engineering. Bivalent antibody pliers inhibit beta-tryptase by an allosteric mechanism dependent on the IgG hinge.,Maun HR, Vij R, Walters BT, Morando A, Jackman JK, Wu P, Estevez A, Chen X, Franke Y, Lipari MT, Dennis MS, Kirchhofer D, Ciferri C, Loyet KM, Yi T, Eigenbrot C, Lazarus RA, Koerber JT Nat Commun. 2020 Dec 22;11(1):6435. doi: 10.1038/s41467-020-20143-x. PMID:33353951 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Tryptase

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