Sec62 Protein Mediates Membrane Insertion and Orientation of Moderately Hydrophobic Signal Anchor Proteins in the Endoplasmic Reticulum (ER)
Sec62 Protein Mediates Membrane Insertion and Orientation of Moderately Hydrophobic Signal Anchor Proteins in the Endoplasmic Reticulum (ER)
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DOI：
10.1074/jbc.m113.473009
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发表时间：
2013-06-21
影响因子：
4.8
通讯作者：
Kim, Hyun
中科院分区：
文献类型：
--
作者：
Reithinger, Johannes H.;Kim, Ji Eun Hani;Kim, Hyun
已知新生链靶向内质网膜的途径是信号识别颗粒(SRP)依赖的共翻译或SRP依赖的翻译后易位途径，取决于信号序列。利用一组携带N-端信号锚序列的疏水性受控的模型和细胞蛋白，以及SRP或Sec62功能缺陷的酵母突变株，系统地评价了疏水性依赖的靶向效率和靶向途径的偏好。我们的结果表明，依赖SRP的共翻译和非SRP依赖的翻译后易位对信号锚蛋白来说并不是相互排斥的，中等疏水性的信号锚蛋白需要SRP和Sec62才能正确地靶向和转运到内质网。此外，Sec62中的缺陷选择性地减少了插入到N-In-C-Out(类型II)膜拓扑中的信号序列，这意味着在易位的早期阶段，Sec62在调节信号序列的方向方面具有未被发现的作用。
Nascent chains are known to be targeted to the endoplasmic reticulum membrane either by a signal recognition particle (SRP)-dependent co-translational or by an SRP-independent post-translational translocation route depending on signal sequences. Using a set of model and cellular proteins carrying an N-terminal signal anchor sequence of controlled hydrophobicity and yeast mutant strains defective in SRP or Sec62 function, the hydrophobicity-dependent targeting efficiency and targeting pathway preference were systematically evaluated. Our results suggest that an SRP-dependent co-translational and an SRP-independent post-translational translocation are not mutually exclusive for signal anchor proteins and that moderately hydrophobic ones require both SRP and Sec62 for proper targeting and translocation to the endoplasmic reticulum. Further, defect in Sec62 selectively reduced signal sequences inserted in an N-in-C-out (type II) membrane topology, implying an undiscovered role of Sec62 in regulating the orientation of the signal sequence in an early stage of translocation.