Conformation of an Endogenous Ligand in a Membrane Bilayer for the Macrophage Scavenger Receptor CD36

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• 作者：Xin-Min Li ; Robert G. Salomon ; Jun Qin ; Stanley L. Hazen
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：May 1, 2007
• 年：2007
• 卷：46
• 期：17
• 页码：5009 - 5017
• 全文大小：163K
• 年卷期：v.46,no.17(May 1, 2007)
• ISSN：1520-4995

文摘

Phagocytic removal of aged or oxidatively damaged cells and macromolecules is anindispensable homeostatic function of the innate immune system. A structurally conserved family ofoxidized phospholipids that serve as endogenous high-affinity ligands for the macrophage scavenger receptorCD36 (oxPC_CD36) was recently identified. Enriched within atherosclerotic plaque and senescent cellmembranes, oxPC_CD36 promote the uptake of oxidized lipoproteins and cell membranes by macrophageswhen present at only a few molecules per particle. How macrophages recognize oxPC_CD36 within cellularmembranes and lipoprotein surfaces remains unknown. Herein, we deduce the conformation of oxPC_CD36near the hydrophobic-hydrophilic interface within membrane bilayers by determining multiple criticalinternuclear distances using nuclear Overhauser enhancement spectroscopy. The molecular model revealsa unique conformation for oxPC_CD36 within bilayers whereby the distal end of the sn-2 acyl chain harboringthe structurally conserved CD36 recognition motif protrudes into the aqueous phase. The remarkableconformation elucidated for oxPC_CD36 produces a surface accessible phagocytic "eat me signal" to facilitatesenescent cell and oxidized lipoprotein recognition by the scavenger receptor CD36 as part of its immunesurveillance function.