Fig. 4: A model for how LCAT binds to HDL.
a, b Activated LCAT (PDB code 6MVD) was docked into each lobe of the 2:1 3D reconstruction with C2 symmetry, with the double belt18 (a) and looped belt30 (b) model for HDL placed in the HDL density. c The model is compatible with the agonist Fab antibody binding to LCAT4. d A close-up of the concave surface that allows lipidic substrate to move in (path shown with arrow) and out of the active site (Ser181 in green) from HDL. The hydrophobic surface expected to bind to HDL is depicted with residues in purple sticks. The N and C terminus are disordered and depicted as dashed lines, which includes a glycosylation site (NAG) at Asn20. A stick model of an LCAT allosteric activator is also shown bound spanning the interface between LCAT and HDL. e The lid from a closed structure in yellow (PDB code 5TXF, with the rest of the lid modeled in), which swings out of the way (see arrow) when LCAT is activated by HDL. In all panels, side chains of crosslinked residues are shown as red spheres, and glycosylation sites as purple spheres for the first sugar. ApoA-I helix 6 is shown in cyan.
