Nickel is a specific inhibitor for the binding of activated alpha 2-macroglobulin to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor.
Nickel is a specific inhibitor for the binding of activated alpha 2-macroglobulin to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor.
复制标题
镍是活性α2-巨球蛋白与低密度脂蛋白受体相关蛋白/α2-巨球蛋白受体结合的特异性抑制剂。
DOI：
10.1021/bi00049a022
复制
发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Tulenko,TN
中科院分区：
文献类型：
--
作者：
Hussain,MM;Kancha,RK;Tulenko,TN
Revised Manuscript ReceivedSeptember 5, 1995® abstract: The low density receptor-related protein/a. 2-macroglobulin receptor (LRP/a. 2-MR) binds to several ligands involved in lipoprotein and protease clearance. The receptor-associated protein (RAP) inhibits the binding of all known ligands. We studied the inhibition by Ni2+ of the binding of different ligands to cells and to the purified LRP/a. 2-MR. Ni2+ inhibited all of the specific binding of radiolabeled methylamine-activated a. 2-macroglobulin (125I-ct2-M*) to rabbit aortic smooth muscle cells (SMC), rat hepatoma Fu5AH, and mouse fibroblast L cells. Ni2+ also inhibited the binding of trypsin-activated a2-macroglobulin to SMC but did not affect the binding of RAP, Pseudomonas exotoxin A, or low-density lipoproteins. The inhibition of 0.2-M* binding byNi2+ was not due to its interaction with Oa-M*. Preincubation of SMC with Ni2+ followed by ligand binding suggested that Ni2+ binds to cell-surface molecules and inhibits the binding of 2-* but does not affect RAP binding. Most of the binding of o2-M* to SMC was due to its binding to the LRP/02-MR, as opposed to the recently described signaling receptor, as demonstrated by the inhibition of this binding by the RAP. Moreover, the inhibition of 0.2-M* binding to the LRP/0L2-MR by Ni2+ was demonstrated using purified receptor immobilized on microtiter plates. Two to three molecules of 63Ni2+ bound to the immobilized receptor with equal affinity but not to 0.2-M*. The specific binding of (X2-M* to the immobilized receptor was inhibited in the presence of nickel. Furthermore, preincubation of the immobilized LRP/012-MR with Ni2+ inhibited the binding of 0.2-M* but did not inhibit RAP or exotoxin A binding. These data suggest that Ni2+ is a site-specific inhibitor for the (X2-M* binding site present on the LRP/012-MR. Nickel may be a useful tool for investigating different ligand binding domains of the LRP/012-MR.Native a2-macroglobulin molecule is a general protease inhibitor that interacts with all four classes of proteases [for reviews, see Sottrup-Jensen (1989), Gonias (1992), and Chu and Pizzo (1994)]. After its interaction with proteases, a2-macroglobulin undergoes a conformational change, resulting in the entrapment of proteases and exposure of a receptor-
