Yamamoto Taichi, Ryan Robert O
Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital, Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Biochem Biophys Res Commun. 2007 Mar 16;354(3):820-4. doi: 10.1016/j.bbrc.2007.01.066. Epub 2007 Jan 22.
Apolipoprotein E (apoE) is a ligand for members of the low-density lipoprotein receptor (LDLR) family. Lipid-free apoE is not recognized by LDLR, yet interaction with lipid confers receptor recognition properties. Although lipid interaction is known to induce a conformational change in apoE, it is not known if the lipid composition of the resulting complex influences binding. Using reconstituted lipoprotein particles of apoE3 N-terminal (NT) domain and dimyristoylphosphatidylcholine (DMPC), maximal LDLR binding was observed at DMPC:apoE3-NT ratios >2.5:1 (w/w). ApoE3-NT lipid particles prepared with egg sphingomyelin were functional as LDLR ligands while complexes formed with the anionic phospholipids dimyristoylphosphatidylglycerol or dimyristoylphosphatidylserine (DMPS) were not. In the case of apoE3-NT, lipid particles comprised of a mixture of DMPC and DMPS, a DMPS concentration dependent inhibition of LDLR binding activity was observed. Thus, in addition to affecting apoE conformational status, the lipid composition of ligand particles can modulate LDLR binding activity.
载脂蛋白E（apoE）是低密度脂蛋白受体（LDLR）家族成员的配体。无脂质的apoE不能被LDLR识别，但与脂质的相互作用赋予了受体识别特性。尽管已知脂质相互作用会诱导apoE发生构象变化，但尚不清楚所得复合物的脂质组成是否会影响结合。使用重组的载脂蛋白E3 N端（NT）结构域脂蛋白颗粒和二肉豆蔻酰磷脂酰胆碱（DMPC），在DMPC:apoE3-NT比例>2.5:1（w/w）时观察到最大的LDLR结合。用鸡蛋鞘磷脂制备的载脂蛋白E3-NT脂质颗粒作为LDLR配体具有功能，而与阴离子磷脂二肉豆蔻酰磷脂酰甘油或二肉豆蔻酰磷脂酰丝氨酸（DMPS）形成的复合物则不具有功能。就载脂蛋白E3-NT而言，由DMPC和DMPS混合物组成的脂质颗粒，观察到DMPS浓度依赖性抑制LDLR结合活性。因此，除了影响apoE的构象状态外，配体颗粒的脂质组成还可以调节LDLR结合活性。
