Berndt Uta, Oellerer Stefan, Zhang Ying, Johnson Arthur E, Rospert Sabine
Institute of Biochemistry and Molecular Biology and Center for Biological Signalling Studies, University of Freiburg, Stefan-Meier-Strasse 17, D-79104 Freiburg, Germany.
Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1398-403. doi: 10.1073/pnas.0808584106. Epub 2009 Jan 21.
Sorting of eukaryotic membrane and secretory proteins depends on recognition of ribosome-bound nascent chain signal sequences by the signal recognition particle (SRP). The current model suggests that the SRP cycle is initiated when a signal sequence emerges from the ribosomal tunnel and binds to SRP. Then elongation is slowed until the SRP-bound ribosome-nascent chain complex (RNC) is targeted to the SRP receptor in the endoplasmic reticulum (ER) membrane. The RNC is then transferred to the translocon, SRP is released, and translation resumes. Because RNCs do not target to the translocon efficiently if nascent chains become too long, the window for SRP to identify its substrates is short. We now show that a transmembrane signal-anchor sequence (SA) significantly enhances binding of SRP to RNCs even before the SA emerges from the ribosomal tunnel. In this mode, SRP does not contact the SA directly but is in close proximity to the portion of the nascent polypeptide that has already left the ribosomal tunnel. Early recruitment of SRP provides a mechanism to expand the window for substrate identification. We suggest that the dynamics of the SRP-ribosome interaction is affected not only by the direct binding of SRP to an exposed signal sequence but also by properties of the translating ribosome that are triggered from within the tunnel.
真核细胞膜蛋白和分泌蛋白的分选取决于信号识别颗粒（SRP）对核糖体结合新生链信号序列的识别。当前模型表明，当信号序列从核糖体隧道中出现并与SRP结合时，SRP循环启动。然后延伸速度减慢，直到与SRP结合的核糖体 - 新生链复合物（RNC）靶向内质网（ER）膜中的SRP受体。接着RNC被转移到易位子，SRP被释放，翻译恢复。由于如果新生链变得太长，RNC不能有效地靶向易位子，所以SRP识别其底物的窗口很短。我们现在表明，跨膜信号锚定序列（SA）甚至在SA从核糖体隧道中出现之前就显著增强了SRP与RNC的结合。在这种模式下，SRP不直接接触SA，而是紧邻已经离开核糖体隧道的新生多肽部分。SRP的早期募集提供了一种扩大底物识别窗口的机制。我们认为，SRP - 核糖体相互作用的动力学不仅受SRP与暴露信号序列直接结合的影响，还受核糖体隧道内触发的翻译核糖体特性的影响。
