铜绿假单胞菌外毒素A与人类Sec61复合物的相互作用抑制了内质网的被动钙外流。
Interaction of Pseudomonas aeruginosa Exotoxin A with the human Sec61 complex suppresses passive calcium efflux from the endoplasmic reticulum.
作者信息
Schäuble Nico, Cavalié Adolfo, Zimmermann Richard, Jung Martin
机构信息
Medical Biochemistry and Molecular Biology; Saarland University; Homburg, Germany.
Experimental and Clinical Pharmacology and Toxicology; Saarland University; Homburg, Germany.
出版信息
Channels (Austin). 2014;8(1):76-83. doi: 10.4161/chan.26526. Epub 2013 Oct 2.
Abstract
According to live-cell calcium-imaging experiments, the Sec61 complex is a passive calcium-leak channel in the human endoplasmic reticulum (ER) membrane that is regulated by ER luminal immunoglobulin heavy chain binding protein (BiP) and cytosolic Ca(2+)-calmodulin. In single channel measurements, the open Sec61 complex is Ca(2+) permeable. It can be closed not only by interaction with BiP or Ca(2+)-calmodulin, but also with Pseudomonas aeruginosa Exotoxin A which can enter human cells by retrograde transport. Exotoxin A has been shown to interact with the Sec61 complex and, thereby, inhibit ER export of immunogenic peptides into the cytosol. Here, we show that Exotoxin A also inhibits passive Ca(2+) leakage from the ER in human cells, and we characterized the N-terminus of the Sec61 α-subunit as the relevant binding site for Exotoxin A.
摘要
根据活细胞钙成像实验，Sec61复合物是人类内质网（ER）膜中的一种被动钙泄漏通道，受内质网腔免疫球蛋白重链结合蛋白（BiP）和胞质Ca(2+)-钙调蛋白调节。在单通道测量中，开放的Sec61复合物对Ca(2+)具有通透性。它不仅可以通过与BiP或Ca(2+)-钙调蛋白相互作用而关闭，还可以与铜绿假单胞菌外毒素A相互作用而关闭，外毒素A可通过逆行转运进入人类细胞。外毒素A已被证明与Sec61复合物相互作用，从而抑制免疫原性肽从内质网向胞质溶胶的输出。在这里，我们表明外毒素A还抑制人类细胞中内质网的被动Ca(2+)泄漏，并且我们将Sec61α亚基的N端鉴定为外毒素A的相关结合位点。
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