The catalytic activity of protein disulfide isomerase is involved in human immunodeficiency virus envelope- mediated membrane fusion after CD4 cell binding
The catalytic activity of protein disulfide isomerase is involved in human immunodeficiency virus envelope- mediated membrane fusion after CD4 cell binding
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DOI：
10.1086/318823
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发表时间：
2001-03-01
影响因子：
6.4
通讯作者：
Miquelis, R
中科院分区：
文献类型：
--
作者：
Fenouillet, E;Barbouche, R;Miquelis, R
蛋白二硫异构酶（PDI）是一种具有巯基二硫还原异构酶活性的多功能蛋白。它催化细胞表面的硫醇-二硫交换反应，可能导致表面蛋白的结构修饰。PDI抑制剂改变人类免疫缺陷病毒（HIV）的传播，并且已经提出PDI可能是触发HIV进入的必要条件。本研究通过细胞-细胞融合实验检验了这一假设，在细胞表面表达的HIV包膜（Env）与CD4（+）淋巴细胞相互作用。PDI聚集在cd4富集区附近的淋巴细胞表面，但两种抗原本质上不共定位。抗pdi抗体及其催化功能的2个抑制剂改变了env介导的cd4细胞结合后的膜融合。淋巴细胞上存在的PDI催化活性是融合所必需的，这一事实支持了催化剂有助于Env内cd4细胞结合后构象变化的假设。
Protein disulfide isomerase (PDI) is a multifunctional protein with thiol-disulfide redox-isomerase activities. It catalyzes thiol-disulfide interchange reactions on the cell surface that may cause structural modifications of exofacial proteins. PDI inhibitors alter human immunodeficiency virus (HIV) spread, and it has been suggested that PDI may be necessary to trigger HIV entry. This study examined this hypothesis by using cell-to-cell fusion assays, in which the HIV envelope (Env) expressed on the cell surface interacts with CD4(+) lymphocytes. PDI is clustered at the lymphocyte surface in the vicinity of CD4-enriched regions, but both antigens essentially do not colocalize. Anti-PDI antibodies and 2 inhibitors of its catalytic function altered Env-mediated membrane fusion at a post-CD4 cell binding step. The fact that the PDI catalytic activity present on lymphocytes is required for fusion supports the hypothesis that catalysts assist post-CD4 cell binding conformational changes within Env.