title: Conformation of an endogenous ligand in a membrane bilayer for the macrophage scavenger receptor CD36.
abstract: 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 (oxPC(CD36)) was recently identified. Enriched within atherosclerotic plaque and senescent cell membranes, oxPC(CD36) promote the uptake of oxidized lipoproteins and cell membranes by macrophages when present at only a few molecules per particle. How macrophages recognize oxPC(CD36) within cellular membranes and lipoprotein surfaces remains unknown. Herein, we deduce the conformation of oxPC(CD36) 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 oxPC(CD36) within bilayers whereby the distal end of the sn-2 acyl chain harboring the structurally conserved CD36 recognition motif protrudes into the aqueous phase. The remarkable conformation elucidated for oxPC(CD36) produces a surface accessible phagocytic "eat me signal" to facilitate senescent cell and oxidized lipoprotein recognition by the scavenger receptor CD36 as part of its immune surveillance function.
authors.affiliation: Department of Cell Biology, and Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
authors.forename: Robert G
authors.initials: RG
authors.lastname: Salomon
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
mesh_terms: D018955:CD36 Antigens / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008051:Lipid Bilayers; D008264:Macrophages / Q000378:metabolism*; D008968:Molecular Conformation; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D018955:CD36 Antigens; D008024:Ligands; D008051:Lipid Bilayers