大约5% 的真核膜蛋白（被称为尾部固定的蛋白或TA蛋白）被一个“C-端跨膜域”固定到类脂双层上。
“Get3 ATP酶”以那些以内质网(ER)为目的地的TA蛋白为目标，而“基质- Get3复合物”则与ER中被称为Get1 和 Get2的两个膜蛋白结合在一起。
在这项研究中，Keenan及其同事用纯化的成分重建了“TA蛋白-插入环”，提出了关键复合物的晶体结构。
结合到伴护分子Get3上的一个TA基质蛋白最初通过与Get2的相互作用被吸收到膜上。一旦被吸收后。Get1便与Get3相互作用，驱动TA蛋白以一种依赖于ATP酶的方式被释放。
这项工作为最小的“TA蛋白-插入环”提供了详细的结构和机制框架。
生物探索推荐英文摘要
The mechanism of membrane-associated steps in tail-anchored protein insertion
Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are chaperoned by cytosolic targeting factors that deliver them to a membrane receptor for insertion. Although a basic framework for TA protein recognition is now emerging, the decisive targeting and membrane insertion steps are not understood. Here we reconstitute the TA protein insertion cycle with purified components, present crystal structures of key complexes between these components and perform mutational analyses based on the structures. We show that a committed targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is initially recruited to the membrane through an interaction with Get2. Once the targeting complex has been recruited, Get1 interacts with Get3 to drive TA protein release in an ATPase-dependent reaction. After releasing its TA protein cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP binding. This work provides a detailed structural and mechanistic framework for the minimal TA protein insertion cycle.
