BINDING OF PERFORIN TO MEMBRANES IS SENSITIVE TO LIPID SPACING AND NOT HEADGROUP

BINDING OF PERFORIN TO MEMBRANES IS SENSITIVE TO LIPID SPACING AND NOT HEADGROUP
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DOI:
10.1016/0165-2478(92)90108-z
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发表时间:
1992-04-01
期刊:
影响因子:
4.4
通讯作者:
WILLIAMSON, P
WILLIAMSON, P
中科院分区:
医学3区
文献类型:
--
作者:
ANTIA, R;SCHLEGEL, RA;WILLIAMSON, P

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当触发时,溶细胞效应细胞(溶细胞T淋巴细胞(CTL)和大颗粒淋巴细胞(LGL))从细胞质颗粒释放效应分子[1,2],包括溶解蛋白穿孔素。这种蛋白质结合并掺入靶细胞的质膜中,在那里它聚集以形成导致靶细胞裂解和死亡的孔。普遍存在的磷脂磷脂酰胆碱(PC)和鞘磷脂的头基磷酸胆碱被认为是穿孔素的特异性受体[3]。我们在这里报告说,任何头基特异性超过磷脂间距在确定结合的穿孔素脂质体。我们还发现,在一个自然的双层,红细胞的质膜,影响细胞的敏感性穿孔素介导的裂解外小叶脂质的间距。最后,我们证明了CTL中的质膜脂质比靶细胞中的更紧密地间隔开,这表明脂质间隔有助于CTL对穿孔素介导的裂解的相对抗性。
When triggered, cytolytic effector cells (cytolytic T-lymphocytes (CTL) and large granular lymphocytes (LGL)) release effector molecules from cytoplasmic granules [1, 2], including the lytic protein perforin. This protein binds and incorporates into the plasma membrane of target cells, where it aggregates to form pores which cause target cell lysis and death. Phosphorylcholine, the headgroup of the ubiquitous phospholipids phosphatidylcholine (PC) and sphingomyelin, has been proposed as the specific receptor for perforin [3]. We report here that any headgroup specificity is outweighed by phospholipid spacing in determining binding of perforin to liposomes. We also find that the spacing of outer leaflet lipids in a natural bilayer, the plasma membrane of the erythrocyte, influences susceptibility of the cell to perforin-mediated lysis. Finally, we demonstrate that the plasma membrane lipids in CTL are more closely spaced than in target cells, suggesting that lipid spacing contributes to the relative resistance of CTL to perforin-mediated lysis.