6gfe

High-resolution Structure of a therapeutic full-length anti-NPRA Antibody with exceptional Conformational Diversity

spinqualitylabelsall models 6gfe, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gfe is a 4 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 1.8Å Ligands: ACT, BMA, CA, FUC, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We report the x-ray crystal structure of intact, full-length human immunoglobulin (IgG4) at 1.8 A resolution. The data for IgG4 (S228P), an antibody targeting the natriuretic peptide receptor A, show a previously unrecognized type of Fab-Fc orientation with a distorted lambda-shape in which one Fab-arm is oriented toward the Fc portion. Detailed structural analysis by x-ray crystallography and molecular simulations suggest that this is one of several conformations coexisting in a dynamic equilibrium state. These results were confirmed by small angle x-ray scattering in solution. Furthermore, electron microscopy supported these findings by preserving molecule classes of different conformations. This study fosters our understanding of IgG4 in particular and our appreciation of antibody flexibility in general. Moreover, we give insights into potential biological implications, specifically for the interaction of human anti-natriuretic peptide receptor A IgG4 with the neonatal Fc receptor, Fcgamma receptors, and complement-activating C1q by considering conformational flexibility. Structure of a Therapeutic Full-Length Anti-NPRA IgG4 Antibody: Dissecting Conformational Diversity.,Blech M, Horer S, Kuhn AB, Kube S, Goddeke H, Kiefer H, Zang Y, Alber Y, Kast SM, Westermann M, Tully MD, Schafer LV, Garidel P Biophys J. 2019 May 7;116(9):1637-1649. doi: 10.1016/j.bpj.2019.03.036. Epub 2019, Apr 5. PMID:31023536 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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