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首页> 外文期刊>The Journal of biological chemistry >Interferon-induced Transmembrane Protein 3 Is a Type II Transmembrane Protein
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Interferon-induced Transmembrane Protein 3 Is a Type II Transmembrane Protein

机译：干扰素诱导的跨膜蛋白3是II型跨膜蛋白

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The interferon-induced transmembrane (IFITM) proteins are a family of small membrane proteins that inhibit the cellular entry of several genera of viruses. These proteins had been predicted to adopt a two-pass, type III transmembrane topology with an intracellular loop, two transmembrane helices (TM1 and TM2), and extracellular N and C termini. Recent work, however, supports an intramembrane topology for the helices with cytosolic orientation of both termini. Here we determined the topology of murine Ifitm3. We found that the N terminus of Ifitm3 could be stained by antibodies at the cell surface but that this conformation was cell type-dependent and represented a minority of the total plasma membrane pool. In contrast, the C terminus was readily accessible to antibodies at the cell surface and extracellular C termini comprised most or all of those present at the plasma membrane. The addition of a C-terminal KDEL endoplasmic reticulum retention motif to Ifitm3 resulted in sequestration of Ifitm3 in the ER, demonstrating an ER-luminal orientation of the C terminus. C-terminal, but not N-terminal, epitope tags were also degraded within lysosomes, consistent with their luminal orientation. Furthermore, epitope-tagged Ifitm3 TM2 functioned as a signal anchor sequence when expressed in isolation. Collectively, our results demonstrate a type II transmembrane topology for Ifitm3 and will provide insight into its interaction with potential targets and cofactors.
机译：干扰素诱导的跨膜（IFITM）蛋白质是一系列小膜蛋白，其抑制几种属病毒的细胞进入。已经预测这些蛋白质采用双通，III型跨膜拓扑，与细胞内环，两个跨膜螺旋（TM1和TM2）和细胞外N和C Termini。然而，最近的工作支持螺旋的intramemmane拓扑，具有两端的细胞源方向。在这里，我们确定了小鼠IFITM3的拓扑。我们发现IFITM3的N末端可以通过细胞表面的抗体染色，但是这种构象是细胞类型依赖性的并且代表总血浆膜池的少数群体。相反，C细胞表面和细胞外C末端的抗体易于易于获得C末端，其包含在质膜上存在的大多数或所有这些。向IFITM3加入C末端kdel内质网保留基序导致ERITM3在ER中螯合，证明了C末端的ER-in-Luminal取向。 C-末端，但不是N-末端，表位标签也在溶酶体中降解，与其腔内取向一致。此外，当以隔离表示时，展位标记的IFITM3 TM2用作信号锚定序列。统称，我们的结果表明IFITM3的II型跨膜拓扑，并将洞察其与潜在目标和辅因子的相互作用。

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