Li Yan, Jain Neeraj, Limpanawat Suweeraya, To Janet, Quistgaard Esben M, Nordlund Par, Thanabalu Thirumaran, Torres Jaume
School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Virology. 2015 Aug;482:105-10. doi: 10.1016/j.virol.2015.03.034. Epub 2015 Apr 2.
The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target.
小疏水(SH)蛋白是一种由人类呼吸道合胞病毒(hRSV)编码的形成通道的短多肽。SH蛋白的缺失导致病毒在小鼠和灵长类动物中减毒,并使感染细胞中的凋亡延迟。我们使用了基于膜的酵母双杂交系统(MbY2H)和来自人肺cDNA的文库来检测与SH蛋白结合的蛋白质。这导致鉴定出一种膜蛋白,即B细胞相关蛋白31(BAP31)。转染的SH蛋白在细胞中与转染的BAP31共定位,并下拉内源性BAP31。在去污剂胶束中用纯化的BAP31 C末端内结构域滴定同位素标记的SH蛋白表明这两种蛋白之间存在直接相互作用。鉴于BAP31在蛋白质运输中的关键作用及其在促凋亡和抗凋亡途径中的关键参与,这种新的相互作用可能构成一个潜在的药物靶点。