Conformation of an endogenous ligand in a membrane bilayer for the macrophage scavenger receptor CD36.

Phagocytic removal of aged or oxidatively damaged cells and macromolecules is an indispensable homeostatic function of the innate immune system. A structurally conserved family of oxidized phospholipids that serve as endogenous high-affinity ligands for the macrophage scavenger receptor CD36 (oxPCCD36) was recently identified. Enriched within atherosclerotic plaque and senescent cell membranes, oxPCCD36 promote the uptake of oxidized lipoproteins and cell membranes by macrophages when present at only a few molecules per particle. How macrophages recognize oxPCCD36 within cellular membranes and lipoprotein surfaces remains unknown. Herein, we deduce the conformation of oxPCCD36 near the hydrophobic−hydrophilic interface within membrane bilayers by determining multiple critical internuclear distances using nuclear Overhauser enhancement spectroscopy. The molecular model reveals a unique conformation for oxPCCD36 within bilayers whereby the distal end of the sn-2 acyl chain harboring the structurally conserv...