Fig. 3: Interaction of MBL with SARS-CoV-2 spike protein through its CRD.
From: Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
a, Binding of MBL to spike protein (Spike-LV) or VSV-g-pseudotyped lentivirus (red dotted line). Data are presented as mean ± s.e.m.; n = 2 independent experiments performed with two to six technical replicates. b, Binding of MBL to spike protein, alone or in the presence of d-mannose, N-acetyl-glucosamine or d-glucose. Data are presented as mean ± s.e.m.; n = 4 independent experiments. c, Trimeric MBL2 model showing the distance (approximately 40 Å) between the binding sites of mannose (white spheres). d, Fourteen mannose-binding sites (red triangles) imposed onto spike protein, where the S1 region (1–685) is green, the beginning of the S2 region (686–815) is black and the S2′ region is white. e, Putative binding site of MBL2. The structure is posed with the highest site-specific probability to be glycosylated with oligomannose. f, The spike–MBL complex. Glycosylation sites are colored according to the oligomannose content: gold, <60%; purple, >80% up until the S2′ region; blue, >80% in the S2′ region. g, Schematic representation of glycosylation sites and nucleotide substitutions in the variant strains identified to date. Oligomannose-glycosylated sites are shown. Single-nucleotide polymorphisms (SNPs) common to all variants are in bold; NTD, N-terminal domain; FP, fusion peptide; HR1 and HR2, heptad repeat 1 and 2; cleavage sites are reported. h, Binding of MBL to SARS-CoV-2 spike protein variants. Data are presented as mean ± s.e.m.; n = 2 independent experiments performed in triplicate. i, Membrane attack complex (MAC) (C5b-9) deposition on spike protein. Data are presented as mean ± s.e.m.; n = 3 of three independent experiments performed in triplicate. Statistical analysis was calculated by two-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test; NHS, normal human serum; HI-NHS, heat-inactivated normal human serum; C1qDHS, C1q-depleted human serum; C4DHS, C4-depleted human serum; C3DHS, C3-depleted human serum; MBL ID, MBL-immunodepleted serum; rhMBL, recombinant human MBL.
