Extended Data Fig. 10: Comparison of LPS coordination in PbgA to known selective and passive LPS-binding proteins.

PbgA (this study), MsbA (PDB code 6BPP), a selective LPS transporter^29,72, LptB₂FG (PDB code 6MHU), a selective LPS^33,75, and TLR4-MD2 (PDB code 3VQ2), a high-affinity LPS receptor^32,76, represent the examples of selective LPS-binding proteins with known structures. In these latter cases, the hydrophobic acyl chains of lipid A are increased and the bivalent and polar nature are the lipid A head group is exploited. Furthermore, note that Arg216 of PbgA, shown in stick representation, does not appear essential for binding LPS in vivo (see Fig. 3c). In addition, FhuA (PDB code 2FCP), found with LPS complexed along the outer leaflet region of this outer membrane protein barrel³⁴, and OmpE36 (PDB code 5FVN), which has also revealed numerous LPS contacts along the barrel³⁵, are shown for completeness and comparison. Notably, analogous to MsbA, LptB2FG and TLR4, hydrophobic and aromatic side chains make several contacts in FhuA and OmpE36 with the acyl chains of lipid A (not shown for clarity) and polar and basic side chains coordinate the bivalent lipid A head group. In all cases, the lipid A coordination schemes are distinct from what is observed in the LPS–PbgA complex (also see Fig. 3).