(a) Sphingosine-out binding mode in which the sphingoid chain of the Cer moiety remains outside the hydrophobic pocket. GLTP is shown complexed with 24:1 GalCer (PDB: 2EUK) (b) Homodimerization of GLTP promoted by the sphingosine-out binding mode. The GLTP monomers and their bound glycolipid dimerize in antiparallel fashion. (c) Schematic representation of GSL interactions involving 18:1 LacCer in the sphingosine-in binding mode (PDB: 1SX6). Lettering indicates interacting GLTP amino acid residues, dashed arrows show hydrogen bonds oriented from donor to acceptor, the gray surface covers lipid atoms interacting with W96 indole group, the colored planes cover lipid regions participating in interchain interaction, gray lettering corresponds to interactions with a neighbor GLTP in the packing-related dimer in the crystal. (d) Schematic of GSL interactions involving 24:1 GalCer in the sphingosine-out binding mode (PDB: 2EUK). The insert shows a schematic of sphingosine–sphingosine interaction of 24:1 GalCer in the dimer. Lettering and colored planes are defined as in (c). The curved arrow indicates a 90° rotation around the horizontal axis, i.e. x-axis, in the view for the inset of (d) compared with (b).