The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A.
The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A.
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DOI：
10.1016/s0021-9258(18)42291-0
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发表时间：
1992-06
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影响因子：
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通讯作者：
M. Kounnas;Randal E. Morris;M. Thompson;Desmond J. Fitzgerald;D. Strickland;C. Saelinger
中科院分区：
文献类型：
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作者：
M. Kounnas;Randal E. Morris;M. Thompson;Desmond J. Fitzgerald;D. Strickland;C. Saelinger
α 2-巨球蛋白受体/低密度脂蛋白受体相关蛋白（α 2 MR/LRP）是一种由515-kDa和85-kDa多肽组成的大细胞表面糖蛋白;该受体被认为负责活化α 2-巨球蛋白和富含apoE的β-极低密度脂蛋白的结合和内吞作用。一种类似的高分子量糖蛋白已被鉴定为假单胞菌外毒素A（PE）的潜在受体。我们证明，α 2 MR/LRP和PE结合糖蛋白具有类似的流动性十二烷基硫酸钠-聚丙烯酰胺凝胶电泳，是免疫学上难以区分的。此外，亲和纯化的α 2 MR/LRP特异性结合PE，但不结合其结合细胞能力缺陷的突变型毒素。39-kDa受体相关蛋白阻断配体与α 2 MR/LRP的结合，也防止PE对小鼠成纤维细胞的结合和随后的毒性。将结合和毒性降低至50%所需的受体相关蛋白的浓度约为14 nM，该值实际上与受体相关蛋白与纯化受体相互作用的KD相同。总体而言，研究强烈表明α 2 MR/LRP负责内化PE。
The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2 MR/LRP) is a large cell-surface glycoprotein consisting of a 515-kDa and an 85-kDa polypeptide; this receptor is thought to be responsible for the binding and endocytosis of activated alpha 2-macroglobulin and apoE-enriched beta-very low density lipoprotein. A similar high molecular weight glycoprotein has been identified as a potential receptor for Pseudomonas exotoxin A (PE). We demonstrate that the alpha 2 MR/LRP and the PE-binding glycoprotein have a similar mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and are immunologically indistinguishable. Furthermore, affinity-purified alpha 2 MR/LRP binds specifically to PE but not to a mutant toxin defective in its ability to bind cells. The 39-kDa receptor-associated protein, which blocks binding of ligands to alpha 2 MR/LRP, also prevents binding and subsequent toxicity of PE for mouse fibroblasts. The concentration of receptor-associated protein that was required to reduce binding and toxicity to 50% was approximately 14 nM, a value virtually identical to the KD measured for the interaction of receptor-associated protein with the purified receptor. Overall, the studies strongly suggest that the alpha 2 MR/LRP is responsible for internalizing PE.