Fig. 6: X-ray structure of the R3DC23 – HR2 complex.
From: Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that clamp the spike at its base
a left: model of full-length prefusion S (6VSB_1_1_269) with superimposition of the R3DC23 – HR2 complex, all shown in molecular surface representation, with N-glycans in stick representation. R3DC23 VHHs are colored in orange, labeled S protein regions: cytoplasmic domain (red; CP), transmembrane domain (gray; TM), heptad repeat 2 (blue; HR2), S2 stem helix (deep pink; SH), heptad repeat 1 (lemon, HR1), central helix and connector domain (pink; CH-CD), the S1 regions encompassing the N-terminal domain (NTD) and receptor binding domain (RBD) (light blue). Right: model of the proteolytically processed postfusion S2 subunit (7E9T70), color coded as in prefusion spike. b Side and axial view (inset) of the R3DC23 – HR2 complex (sand and blue, respectively) superimposed with prefusion HR2 coiled-coil (light blue). In R3DC23, CDR1, 2, and 3 are colored magenta, yellow, and cyan, respectively. The HR2-binding epitope spanning D1192 – Y1206 is shown in stick representation. c Close-up of boxed region, encompassing a single VHH and two HR2 copies (i and ii) forming the adjoined binding epitope. Escape mutant positions are labeled in red. d Axial view of HR1-HR2 (lemon and blue) region of postfusion S protein, superimposed with R3DC23 in the HR2 complex (gray). e The amino acids involved in interactions between R3DC23 and two HR2 helices as observed in the crystal of the R3DC23-HR2 complex are indicated in red.
