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Figure 5.
Fig. 5. Model representation of the interaction between bnmAb
2F5 and HIV-1 gp41. This figure was generated by performing a
positional overlap of the 2F5 F[ab]′–gp41 epitope peptide
^514GIGALFLGFLGAAGS^528KK-Ahx-^655KNEQELLELDKWASLWN^671 crystal
structure (PDB ID 3D0L) with the gp41 MPER
^662ELDKWASLWNWFNITNWLWYIK^683 structure in a lipid environment
obtained by NMR/EPR/surface plasmon resonance (represented in
yellow; PDB ID 2PV6) and presented by Sun et al.^38 The 2F5
epitope is represented in green, and the 2F5 F[ab]′ fragment
is depicted as a vacuum electrostatic model, with blue
indicating positively charged regions and with red indicating
negatively charged regions; white represents nonpolar regions of
the molecule. The orientation of the bnmAb 2F5 relative to the
viral membrane is chosen based on assigning the position of the
sulfate ion (in the green circle) to overlap with the headgroups
of the viral membrane, the electrostatic charges on the surface
of the F[ab]′, and the overlap of the α-helical MPER
structures of the two models. Then, the mobile CDR H3 extended
loop points towards the membrane, where it is hypothesized to
interact with components of the membrane bilayer or with other
parts of gp41 residing in or near the membrane. As there is no
information available about the exact conformation of HR1, HR2,
and FP of gp41 when binding to bnmAb 2F5, these parts have not
been included in the model. The inset box shows a magnification
of the 2F5 F[ab]′ interaction with its gp41 epitope. It
displays the key residues of the 2F5 paratope (mostly CDR
residues) involved in mediating the interaction with its antigen.
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