Stability and function of the Sec61 translocation complex depends on the Sss1p tail-anchor sequence.
Stability and function of the Sec61 translocation complex depends on the Sss1p tail-anchor sequence.
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DOI：
10.1042/bj20101865
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Andrews DW
中科院分区：
文献类型：
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作者：
Falcone D;Henderson MP;Nieuwland H;Coughlan CM;Brodsky JL;Andrews DW
Sss 1 p是内质网（ER）中异源三聚体Sec 61复合物的重要组成部分，是一种尾部锚定蛋白，其确切的作用机制在很大程度上尚不清楚。尾锚定蛋白参与许多细胞过程，其特征在于羧基末端或羧基末端附近的单一跨膜序列（TMS）。Sec 61复合物是分泌蛋白和膜蛋白转位进入和穿过ER膜的分子机器。为了了解Sss 1 p尾锚的功能，我们将突变引入尾锚序列并分析所得酵母表型。点突变的C-末端疏水核心的尾部锚的Sss 1 p被确定，允许Sss 1 p组装成Sec 61复合物，但导致减少的增长，在共同和翻译后易位的缺陷，减少核糖体结合Sec 61复合物，降低稳定性的异源三聚体Sec 61和七聚体Sec复合物，和一个完整的崩溃ER结构。由突变引起的潜在缺陷涉及Sss 1 p尾锚序列对于异源三聚体Sec 61和七聚体Sec复合物的稳定功能的丧失。这些数据表明，通过稳定多蛋白膜复合物，尾部-锚序列的疏水核心可以超过简单的膜锚。
Sss1p, an essential component of the heterotrimeric Sec61 complex in the endoplasmic reticulum (ER) #, is a tail-anchored protein whose precise mechanism of action is largely unknown. Tail-anchored proteins are involved in many cellular processes and are characterized by a single transmembrane sequence (TMS) at or near the carboxyl-terminus. The Sec61 complex is the molecular machine through which secretory and membrane proteins translocate into and across the ER membrane. To understand the function of the tail-anchor of Sss1p, we introduced mutations into the tail-anchor sequence and analyzed the resulting yeast phenotypes. Point mutations in the C-terminal hydrophobic core of the tail-anchor of Sss1p were identified that allowed Sss1p assembly into Sec61 complexes but resulted in diminished growth, defects in co- and post-translational translocation, diminished ribosome binding to Sec61 complexes, reduced stability of both heterotrimeric Sec61 and heptameric Sec complexes, and a complete breakdown of ER structure. The underlying defect caused by the mutations involves loss of a stabilizing function of the Sss1p tail-anchor sequence for both the heterotrimeric Sec61 and the heptameric Sec complexes. These data indicate that by stabilizing multiprotein membrane complexes, the hydrophobic core of a tail-anchor sequence can be more than a simple membrane anchor.