INHIBITION OF A REDUCTIVE FUNCTION OF THE PLASMA-MEMBRANE BY BACITRACIN AND ANTIBODIES AGAINST PROTEIN DISULFIDE-ISOMERASE

被引:205
作者
MANDEL, R [1 ]
RYSER, HJP [1 ]
GHANI, F [1 ]
WU, M [1 ]
PEAK, D [1 ]
机构
[1] BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118
关键词
DIPHTHERIA TOXIN; THIOL DISULFIDE INTERCHANGE; SURFACE-BOUND PROTEINS; ENDOCYTOSIS;
D O I
10.1073/pnas.90.9.4112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Evidence had been provided that a disulfide-linked [I-125]iodotyramine/poly(D-lysine) conjugate was reductively cleaved when bound nonspecifically to the surface of Chinese hamster ovary (CHO) cells and that this cleavage was abolished by membrane-impermeant sulfhydryl blockers. The same blockers were subsequently found to inhibit the cytotoxicity of diphtheria toxin, a disulfide-linked heterodimer that binds to a specific surface receptor and must undergo chain separation to exert its cytotoxicity. This suggested that the disulfides of both macromolecules might be cleaved by a thiol-disulfide interchange reaction, possibly mediated by protein disulfide-isomerase (PDI, EC 5.3.4.1). We tested whether inhibitors of PDI-in particular, bacitracin and anti-PDI antibodies-might mimic the two effects of sulfhydryl blockers. Both bacitracin and anti-PDI antibodies were effective in inhibiting both reductive processes. This strongly suggests that the disulfide cleavage in the two membrane-bound macromolecules is mediated by PDI and that this enzyme, besides its known retention in the endoplasmic reticulum, must also be exposed at the plasma membrane. This paper points to other potentially important disulfide reductions that might be catalyzed by surface-associated PDI. It thereby broadens the known functions of an enzyme already known for its multifunctional properties.
引用
收藏
页码:4112 / 4116
页数:5
相关论文
共 28 条