Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies
Figure 3
Crystal structure of the PRCV RBD bound to the pAPN ectodomain.
A. The dimeric PRCV RBD-pAPN complex in the crystals. Ribbon drawings of the pAPN molecules are shown with domains (D) in orange (N-terminal DI), yellow (DII), red (DIII) and green (C-terminal DIV), and the N-terminal end (n) near the cell membrane. The RBD is shown as ribbon and surface drawings in blue and cyan, with the pAPN-binding Tyr and Trp residues at the RBD tip in red. Location of the remaining CoV S is indicated at the RBD terminal end. Glycans are shown as sticks with carbons in yellow and the zinc ion at the pAPN catalytic site as a cyan sphere. B. Detail of the RBD β1–β2 region with the exposed Tyr residue interacting with the pAPN. Side chains of RBD and pAPN residues engaged in the interaction are shown as sticks with carbons in magenta or green, respectively. NAG7361 glycan N-linked to pAPN Asn736 is shown with carbons in yellow and the electron density map, determined without the glycan, shown as a blue mesh contoured at 3 sigma. C. Detail of the RBD β3–β4 region with the Trp residue interacting with the pAPN. In B and C, RBD residues are numbered following the TGEV sequence shown in D, and intermolecular hydrogen bonds are shown as dashed red lines. D. Structure-based sequence alignment of the TGEV and PRCV RBDs. β-strands are marked with bars. TGEV sequence is numbered. In red, 1AF10 mAb- (for TGEV) and pAPN receptor-binding residues (for PRCV) identified by the structures. Residues absent in the RBD structures are in grey, and the thrombin recognition sequences at the end of recombinant porcine CoV RBDs are in lowercase letters.
