Novel Pathways of Membrane Protein Insertion

最近，我们发现了一种胞质TMD识别复合体(TRC)，它可以选择性地与内质网膜上的TA蛋白相互作用。TRC的一个中心成分被确定为高度保守的40kD ATPase，并代表了这一广泛使用的膜蛋白插入途径的第一分子因子(2)。其他与TRC40合作介导选择性识别、靶向和将TA蛋白插入内质网的成分尚不清楚。我们现在正在采取各种方法来确定这些额外的因子(S)，并重新构建针对具有特定组成的TA蛋白的靶向反应。实现这些目标将确定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.