Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
J Mol Biol. 2012 Nov 2;423(4):600-12. doi: 10.1016/j.jmb.2012.07.023. Epub 2012 Aug 4.
Cotranslational targeting of membrane proteins is mediated by the universally conserved signal recognition particle (SRP). In eukaryotes, SRP attenuates translation during targeting; however, in prokaryotes, a simplified SRP is believed to carry out targeting during continuing translation. Here, we show a detailed stepwise analysis of the targeting of subunit c of the F(0) component of the bacterial ATP synthase (F(0)c) to the inner membrane. We show that the first transmembrane (TM) signal-anchor domain of F(0)c forms a compacted structure within the distal portion of the ribosome tunnel. This structure is formed just prior to the interaction with SRP. In the absence of SRP this structure is lost as the TM domain exits the tunnel; however in the presence of SRP it is stabilized. Our results suggest differences in early protein folding of substrates for prokaryotic SRP-dependent membrane protein targeting pathways, from that of eukaryotic SRP targeting. These results imply that early TM domain recognition by targeting factors acts to ensure that the efficiency of membrane targeting is maintained.
翻译膜蛋白的共翻译靶向是由普遍保守的信号识别颗粒（SRP）介导的。在真核生物中，SRP 在靶向过程中减弱翻译；然而，在原核生物中，简化的 SRP 被认为在持续翻译过程中进行靶向。在这里，我们展示了对细菌 ATP 合酶（F(0)c）的 F(0) 亚基 c 的靶向的详细逐步分析。我们表明，F(0)c 的第一个跨膜（TM）信号锚定结构域在核糖体隧道的远端形成一个紧凑的结构。在与 SRP 相互作用之前形成该结构。在没有 SRP 的情况下，该结构会随着 TM 结构域离开隧道而丢失；然而，在存在 SRP 的情况下，它会被稳定。我们的结果表明，与真核生物 SRP 靶向相比，原核生物 SRP 依赖性膜蛋白靶向途径的底物的早期蛋白质折叠存在差异。这些结果表明，靶向因子对早期 TM 结构域的识别作用确保了膜靶向的效率得以维持。
