Membrane Protein TM Segments Are Retained at the Translocon during Integration until the Nascent Chain Cues FRET-Detected Release into Bulk Lipid
Membrane Protein TM Segments Are Retained at the Translocon during Integration until the Nascent Chain Cues FRET-Detected Release into Bulk Lipid
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DOI：
10.1016/j.molcel.2012.08.023
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发表时间：
2012-11-09
期刊：
影响因子：
16
通讯作者：
Johnson, Arthur E.
中科院分区：
文献类型：
--
作者：
Hou, Bo;Lin, Pen-Jen;Johnson, Arthur E.
大多数膜蛋白在易位子处共翻译整合到内质网膜中，人们普遍认为非极性新生蛋白跨膜片段（TMS）直接分配到非极性膜内部。然而，监测荧光标记 TMS 和散装脂质中扩散的荧光磷脂之间分离的 FRET 方法表明，TMS 不会立即进入膜的脂质相。相反，TMS 通过蛋白质-蛋白质相互作用保留在易位子上，直到翻译终止或在某些情况下通过另一个新生链 TMS 到达易位子触发它们释放到大量脂质中。因此，新生链状态和结构元件通过改变 TMS 和侧翼序列与易位子、核糖体和相关蛋白的相互作用来决定 TMS 释放到脂质相的时间，从而控制连续 TMS 在双层和 TMS 描绘的环折叠中组装的时间。
Most membrane proteins are integrated cotranslationally into the ER membrane at the translocon, where nonpolar nascent protein transmembrane segments (TMSs) are widely believed to partition directly into the nonpolar membrane interior. However, a FRET approach that monitors the separation between a fluorescent-labeled TMS and fluorescent phospholipids diffusing in the bulk lipid reveals that TMSs do not immediately enter the lipid phase of the membrane. Instead, TMSs are retained at the translocon by protein-protein interactions until their release into bulk lipid is triggered by translation termination or, in some cases, by the arrival of another nascent chain TMS at a translocon. Nascent chain status and structural elements therefore dictate the timing of TMS release into the lipid phase by altering TMS and flanking sequence interactions with translocons, ribosomes, and associated proteins, thereby controlling when successive TMSs assemble in the bilayer and TMS-delineated loops fold.