Goder Veit, Spiess Martin
Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
EMBO J. 2003 Jul 15;22(14):3645-53. doi: 10.1093/emboj/cdg361.
We have analyzed in vivo how model signal sequences are inserted and oriented in the membrane during cotranslational integration into the endoplasmic reticulum. The results are incompatible with the current models of retention of positive flanking charges or loop insertion of the polypeptide into the translocon. Instead they indicate that these N-terminal signals initially insert head-on with a cytoplasmic C-terminus before they invert their orientation to translocate the C-terminus. The rate of inversion increases with more positive N-terminal charge and is reduced with increasing hydrophobicity of the signal. Inversion may proceed for up to approximately 50 s, when it is terminated by a signal-independent process. These findings provide a mechanism for the topogenic effects of flanking charges as well as of signal hydrophobicity.
我们已经在体内分析了模型信号序列在共翻译整合到内质网过程中是如何插入膜并定向的。结果与当前关于侧翼正电荷保留或多肽环插入转运体的模型不相符。相反，这些结果表明，这些N端信号最初以细胞质C端头朝里的方式插入，然后才反转其方向以转运C端。反转速率随着N端电荷更正而增加，随着信号疏水性增加而降低。反转可能持续约50秒，然后由一个信号独立的过程终止。这些发现为侧翼电荷以及信号疏水性的拓扑效应提供了一种机制。
