Novel Pathways of Membrane Protein Insertion

最近，我们发现了一个细胞溶质TMD识别复合物（TRC），选择性地与TA蛋白的ER膜的目的相互作用。TRC的中心组分被鉴定为高度保守的40 kD ATP酶，并且代表了这种广泛使用的膜蛋白插入途径中的第一个分子因子（2）。与TRC 40合作介导TA蛋白选择性识别、靶向和插入ER的其他成分尚不清楚。我们现在正在采取各种方法来鉴定这些额外的因子，并用确定的组分重建TA蛋白的靶向反应。实现这些目标将定义基本蛋白质运输途径的核心机制和功能，并为未来的机制和结构分析铺平道路。

Recently, we discovered a cytosolic TMD recognition complex (TRC) that selectively interacts with TA proteins destined for the ER membrane. A central component of TRC was identified as a highly conserved 40 kD ATPase and represents the first molecular factor in this widely used membrane protein insertion pathway (2). Other components that collaborate with TRC40 to mediate selective recognition, targeting, and insertion of TA proteins into the ER are unknown. We are now taking various approaches to identify these additional factor(s) and reconstitute the targeting reaction for TA proteins with defined components. Achieving these goals will define the core machinery and functions for a fundamental protein trafficking pathway and pave the way for future mechanistic and structural analyses.