Cryo-EM structures reveal axe-like modes of V2 apex recognition to be a reproducible antibody extended class in rhesus macaques. (a) Top: Cryo-EM reconstruction of 41328-a.01 in complex with BG505 DS-SOSIP at 2.9-Å resolution. The 41328-a.01 heavy and light chains are colored blue and gray, respectively. Envelope gp120, gp41, and N-linked glycans are colored turquoise, pink, and purple, respectively. Middle: Expanded interface view of 41328-a.01 from the top panel to highlight binding position and interactions with apical envelope glycans. Glycans bound by 41328-a.01 are shown in stick representation with transparent surfaces. Bottom: Further expanded interface view of 41328-a.01 to highlight interactions with apical envelope residues. Interacting residues are depicted in stick representation. Residues at positions corresponding to the conserved five-residue DH3-15*01 gene motif are colored dark red, while the remaining D gene residues are colored pink. Conserved motif position labels are italicized when subjected to SHM. Nitrogen atoms are colored blue, and oxygen atoms are colored bright red. Hydrogen bonds and salt bridges (distance < 3.3 Å) are depicted with dashed lines. The orientations of the C-strand and HCDR3 β-strand mainchain interactions are labeled in the top left corner. (b) Top: Cryo-EM reconstruction of V033-a.01 in complex with BG505 DS-SOSIP at 3.1-Å resolution. The V033-a.01 heavy chain is colored orange, and the remainder of the complex is colored similarly to panel a. Middle: Expanded interface view of V033-a.01 from the top panel to highlight binding position and apical glycan interactions is shown similarly to panel a. Bottom: Further expanded interface view of V033-a.01 to highlight apical residue interactions is shown similarly to panel a. (c) Right: Expanded HCDR3 interface view of CH03 (PDB ID 5ESV) to highlight apical residue interactions is shown similarly to panel A. Left: Expanded HCDR3 interface side view of the alignment of SOSIP complex structures of 41328-a.01 and V033-a.01 determined here to an envelope complex with human Fab PG9 (PDB ID 8FL1) and V1V2–scaffold complex with human Fab CH03 (PDB ID 5ESV). Alignments were made with the V1V2 region from each complex. Only gp120 of the 41328-a.01 complex is shown for clarity.
Figure 4.

Cryo-EM structures reveal axe-like modes of V2 apex recognition to be a reproducible antibody extended class in rhesus macaques. (a) Top: Cryo-EM reconstruction of 41328-a.01 in complex with BG505 DS-SOSIP at 2.9-Å resolution. The 41328-a.01 heavy and light chains are colored blue and gray, respectively. Envelope gp120, gp41, and N-linked glycans are colored turquoise, pink, and purple, respectively. Middle: Expanded interface view of 41328-a.01 from the top panel to highlight binding position and interactions with apical envelope glycans. Glycans bound by 41328-a.01 are shown in stick representation with transparent surfaces. Bottom: Further expanded interface view of 41328-a.01 to highlight interactions with apical envelope residues. Interacting residues are depicted in stick representation. Residues at positions corresponding to the conserved five-residue DH3-15*01 gene motif are colored dark red, while the remaining D gene residues are colored pink. Conserved motif position labels are italicized when subjected to SHM. Nitrogen atoms are colored blue, and oxygen atoms are colored bright red. Hydrogen bonds and salt bridges (distance < 3.3 Å) are depicted with dashed lines. The orientations of the C-strand and HCDR3 β-strand mainchain interactions are labeled in the top left corner. (b) Top: Cryo-EM reconstruction of V033-a.01 in complex with BG505 DS-SOSIP at 3.1-Å resolution. The V033-a.01 heavy chain is colored orange, and the remainder of the complex is colored similarly to panel a. Middle: Expanded interface view of V033-a.01 from the top panel to highlight binding position and apical glycan interactions is shown similarly to panel a. Bottom: Further expanded interface view of V033-a.01 to highlight apical residue interactions is shown similarly to panel a. (c) Right: Expanded HCDR3 interface view of CH03 (PDB ID 5ESV) to highlight apical residue interactions is shown similarly to panel A. Left: Expanded HCDR3 interface side view of the alignment of SOSIP complex structures of 41328-a.01 and V033-a.01 determined here to an envelope complex with human Fab PG9 (PDB ID 8FL1) and V1V2–scaffold complex with human Fab CH03 (PDB ID 5ESV). Alignments were made with the V1V2 region from each complex. Only gp120 of the 41328-a.01 complex is shown for clarity.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal