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首页> 外文期刊>Journal of Molecular Biology >Orientation of internal signal-anchor sequences at the sec61 translocon
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Orientation of internal signal-anchor sequences at the sec61 translocon

机译：内部信号锚序列在sec61易位子上的定位

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摘要

Translocation and insertion of secretory and membrane proteins at the endoplasmic reticulum are mediated by the Sec61 translocon. Evidence from in vivo as well as in vitro experiments indicates that N-terminal signal-anchor sequences initially insert N-first before they invert their orientation to translocate the C-terminus. Inversion is driven by flanking charges according to the positive-inside rule and inhibited by increased signal hydrophobicity. Here, we show that upon extending the N-terminal hydrophilic domain preceding the signal core to more than ~ 20 residues, the insertion behavior changes. Apparent signal inversion and the effect of hydrophobicity are largely lost, suggesting that N-first insertion is limited to N-terminal signal anchors. Extended N-domains sterically hinder N-translocation in a length-dependent manner also for reverse signal anchors with inverted flanking charges. The results indicate a mechanistic difference in the insertion process of N-terminal and internal signal sequences.
机译：内质网分泌蛋白和膜蛋白的转运和插入是由Sec61 translocon介导的。来自体内和体外实验的证据表明，N端信号锚序列最初在插入N-first之前先反转其方向以使C端易位。反转是根据正内规则由侧翼电荷驱动，并受到信号疏水性增加的抑制。在这里，我们表明在将信号核心之前的N端亲水域扩展到超过约20个残基时，插入行为会发生变化。明显的信号反转和疏水性的影响消失了，这表明N-first插入仅限于N-末端信号锚。对于具有反向侧电荷的反向信号锚，延伸的N结构域以长度依赖的方式在空间上阻碍N移位。结果表明在N端和内部信号序列的插入过程中存在机械差异。

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