Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Nat Struct Mol Biol. 2012 Oct;19(10):1018-22. doi: 10.1038/nsmb.2376. Epub 2012 Sep 23.
Membrane proteins destined for insertion into the inner membrane of bacteria or the endoplasmic reticulum membrane in eukaryotic cells are synthesized by ribosomes bound to the bacterial SecYEG or the homologous eukaryotic Sec61 translocon. During co-translational membrane integration, transmembrane α-helical segments in the nascent chain exit the translocon through a lateral gate that opens toward the surrounding membrane, but the mechanism of lateral exit is not well understood. In particular, little is known about how a transmembrane helix behaves when entering and exiting the translocon. Using translation-arrest peptides from bacterial SecM proteins and from the mammalian Xbp1 protein as force sensors, we show that substantial force is exerted on a transmembrane helix at two distinct points during its transit through the translocon channel, providing direct insight into the dynamics of membrane integration.
定位于插入细菌内膜或真核细胞内质网膜的膜蛋白由结合在细菌 SecYEG 或同源真核 Sec61 易位子上的核糖体合成。在共翻译膜整合过程中，新生肽链中的跨膜α-螺旋片段通过朝向周围膜的侧向门从易位子中穿出，但侧向出口的机制尚不清楚。特别是，人们对跨膜螺旋在进入和离开易位子时的行为知之甚少。我们使用细菌 SecM 蛋白和哺乳动物 Xbp1 蛋白的翻译阻断肽作为力传感器，表明在跨膜螺旋通过易位子通道的过程中，在两个不同的点上对其施加了相当大的力，这为膜整合的动力学提供了直接的见解。
