8f8x

Crystal structure of Nb.X0 bound to the afucosylated human IgG1 fragment crystal form II

spinqualitylabelsall models 8f8x, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8f8x is a 4 chain structure with sequence from Camelidae mixed library and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: BMA, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6MZV7_HUMAN Publication Abstract from PubMed Immunoglobulin G (IgG) antibodies contain a complex N-glycan embedded in the hydrophobic pocket between its heavy chain protomers. This glycan contributes to the structural organization of the Fc domain and determines its specificity for Fcgamma receptors, thereby dictating distinct cellular responses. The variable construction of this glycan structure leads to highly-related, but non-equivalent glycoproteins known as glycoforms. We previously reported synthetic nanobodies that distinguish IgG glycoforms. Here, we present the structure of one such nanobody, X0, in complex with the Fc fragment of afucosylated IgG1. Upon binding, the elongated CDR3 loop of X0 undergoes a conformational shift to access the buried N-glycan and acts as a 'glycan sensor', forming hydrogen bonds with the afucosylated IgG N-glycan that would otherwise be sterically hindered by the presence of a core fucose residue. Based on this structure, we designed X0 fusion constructs that disrupt pathogenic afucosylated IgG1-FcgammaRIIIa interactions and rescue mice in a model of dengue virus infection. Mechanism of glycoform specificity and in vivo protection by an anti-afucosylated IgG nanobody.,Gupta A, Kao KS, Yamin R, Oren DA, Goldgur Y, Du J, Lollar P, Sundberg EJ, Ravetch JV Nat Commun. 2023 May 18;14(1):2853. doi: 10.1038/s41467-023-38453-1. PMID:37202422 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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