FIGURE 9.

Surface topography of predicted membrane docking site of HET-C2 and sugar headgroup recognition site of HET-C2 and GLTP. A, HET-C2 orientation and positioning during membrane docking. The OPM computational approach (57) was used to identify residues involved in the initial docking of HET-C2 with the membrane interface. The lipid molecules comprising half of the membrane are shown as lavender-colored with wavy lines representing the lipid hydrocarbon chains. HET-C2 helices are cyan-colored, and important side chain residues are shown in magenta. B, surface hydrophobicity of HET-C2 (Protein Data Bank code 3KV0). Mapping was performed using Chimera (58, 59), which relies on the Kyte-Doolittle scale to rank amino acid hydrophobicity, with blue indicating most hydrophilic, white equaling 0.0, and orange-red being most hydrophobic. The dotted black line corresponds to the membrane interface oriented as shown in A. C, surface topology of the GSL sugar headgroup binding site of HET-C2. Surface residue color reflects charge status (red, negative; blue, positive; white, neutral). To provide spatial relationships reflecting the situation in wild type HET-C2, the exogenous dimethyl group added to Lys⁷³ to facilitate HET-C2 crystallization is not shown. Glu¹⁰⁵, Thr¹⁰², and His¹⁰¹ obstruct the surface adjacent to Trp¹⁰⁹. D, surface topology of the GSL sugar headgroup binding site of human GLTP. Surface residue color reflects charge status (red, negative; blue, positive; white, neutral) for the GLTP-18:1 LacCer complex (Protein Data Bank code 1SX6) (9). 18:1 LacCer is depicted in gold with the hydrocarbon chains of ceramide (left) disappearing into the hydrophobic tunnel. The open, unobstructed surface adjacent to Trp⁹⁶ allows for broader selectivity for binding of various glycolipids.