Fig. 3: A similar binding mode but a disfavored MPER-approach angle of Fab460 compared to patient-derived Fabs from 2F5 and m66.
a Ribbon diagram of Fab460 in complex with MPER-N. Heavy chain, light chain and MPER-N are colored in yellow, orange and magenta, respectively. MPER residue W670 is drawn in stick representation to indicate the MPER-N helix orientation. The β-turn within MPER-N is displayed in pink. The two residues, R40L and E164L, that form a salt bridge between the VL and CL domains are also highlighted in stick representation. The sidechain of E164L in the Fab460/MPER-N complex structure is disordered. Its position in the complex shown in the figure is modeled based on the Apo crystal structure for the purpose of illustration. b The interaction pattern of Fab460 with MPER-N. The MPER-N and major interacting paratope residues from Fab460 are shown in stick representation. Hydrogen bonds and salt bridges are shown as gray dashed lines except for the hydrogen bond in the β-turn, which is shown in green. All β-strands and CDR loops are labeled. c Similarity of the β-turns found in the MPER peptides in their respective structures in complex with 2F5, m66 and Fab460. MPER residue W670 is drawn in stick representation to indicate the orientation of the MPER-N helix. d A superposition of three Fab/MPER complex structures (on the right) based on their common MPER β-turns. The MPER helical part in the Fab460/MPER-N structure is selected to represent the N-terminal helix of the MPER that dynamically moves off the membrane. The selection of the lifting angle of MPER-N helix (~30°) on the membrane is consistent with cryo-EM data (10). The MPER C-terminal helix is not shown in the figure.
