Piguet V, Chen Y L, Mangasarian A, Foti M, Carpentier J L, Trono D
Department of Genetics and Microbiology, Centre Medical Universitaire, 1, rue Michel-Servet, 1211 Geneve 4, Switzerland.
EMBO J. 1998 May 1;17(9):2472-81. doi: 10.1093/emboj/17.9.2472.
The Nef protein of primate lentiviruses down-regulates the cell surface expression of CD4 and probably MHC I by connecting these receptors with the endocytic machinery. Here, we reveal that Nef interacts with the mu chains of adaptor complexes, key components of clathrin-coated pits. For human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) Nef, this interaction occurs via tyrosine-based motifs reminiscent of endocytosis signals. Mutating these motifs prevents the binding of SIV Nef to the mu chain of plasma membrane adaptor complexes, abrogates its ability to induce CD4 internalization, suppresses the accelerated endocytosis of a chimeric integral membrane protein harboring Nef as its cytoplasmic domain and confers a dominant-negative phenotype to the viral protein. Taken together, these data identify mu adaptins as downstream mediators of the down-modulation of CD4, and possibly MHC I, by Nef.
灵长类慢病毒的Nef蛋白通过将这些受体与内吞机制相连，下调CD4以及可能的MHC I的细胞表面表达。在此，我们揭示Nef与衔接蛋白复合体的μ链相互作用，衔接蛋白复合体是网格蛋白包被小窝的关键组分。对于2型人类免疫缺陷病毒（HIV-2）和猿猴免疫缺陷病毒（SIV）的Nef而言，这种相互作用通过类似于内吞信号的基于酪氨酸的基序发生。突变这些基序可阻止SIV Nef与质膜衔接蛋白复合体的μ链结合，消除其诱导CD4内化的能力，抑制以Nef为胞质结构域的嵌合整合膜蛋白的加速内吞作用，并赋予该病毒蛋白显性负性表型。综上所述，这些数据确定μ衔接蛋白是Nef对CD4以及可能的MHC I进行下调作用的下游介质。
