Institute for Biophysical Chemistry, Centre for Biomolecular Magnetic Resonance, Goethe University, D-60325 Frankfurt am Main, Germany.
Science. 2011 Aug 5;333(6043):758-62. doi: 10.1126/science.1207125. Epub 2011 Jun 30.
Tail-anchored (TA) proteins are involved in cellular processes including trafficking, degradation, and apoptosis. They contain a C-terminal membrane anchor and are posttranslationally delivered to the endoplasmic reticulum (ER) membrane by the Get3 adenosine triphosphatase interacting with the hetero-oligomeric Get1/2 receptor. We have determined crystal structures of Get3 in complex with the cytosolic domains of Get1 and Get2 in different functional states at 3.0, 3.2, and 4.6 angstrom resolution. The structural data, together with biochemical experiments, show that Get1 and Get2 use adjacent, partially overlapping binding sites and that both can bind simultaneously to Get3. Docking to the Get1/2 complex allows for conformational changes in Get3 that are required for TA protein insertion. These data suggest a molecular mechanism for nucleotide-regulated delivery of TA proteins.
尾部锚定（TA）蛋白参与包括运输、降解和凋亡在内的细胞过程。它们含有一个 C 端膜锚，并通过与异源寡聚 Get1/2 受体相互作用的 Get3 腺苷三磷酸酶被翻译后递送至内质网（ER）膜。我们已经确定了 Get3 与 Get1 和 Get2 的胞质结构域在不同功能状态下的晶体结构，分辨率分别为 3.0、3.2 和 4.6 埃。结构数据以及生化实验表明，Get1 和 Get2 使用相邻的、部分重叠的结合位点，并且两者都可以同时结合 Get3。与 Get1/2 复合物对接允许 Get3 发生构象变化，这对于 TA 蛋白插入是必需的。这些数据为核苷酸调节 TA 蛋白递呈的分子机制提供了线索。
