A signal-anchor sequence stimulates signal recognition particle binding to ribosomes from inside the exit tunnel
A signal-anchor sequence stimulates signal recognition particle binding to ribosomes from inside the exit tunnel
复制标题
DOI：
10.1073/pnas.0808584106
复制
发表时间：
2009-02-03
影响因子：
11.1
通讯作者：
Rospert, Sabine
中科院分区：
文献类型：
--
作者：
Berndt, Uta;Oellerer, Stefan;Rospert, Sabine
真核生物膜和分泌蛋白的分选依赖于信号识别粒子（SRP）对核糖体结合的新生链信号序列的识别。目前的模型表明，当一个信号序列从核糖体通道中出现并与SRP结合时，SRP周期就开始了。然后延长减慢，直到SRP结合的核糖体-新生链复合体（RNC）靶向内质网（ER）膜中的SRP受体。RNC随后被转移到转座子，SRP被释放，翻译继续进行。因为如果新生链变得太长，rna就不能有效地靶向转座子，因此SRP识别底物的窗口很短。我们现在表明，跨膜信号锚序列（SA）可以显著增强SRP与rna的结合，甚至在SA从核糖体通道中出现之前。在这种模式下，SRP不直接接触SA，而是靠近已经离开核糖体通道的新生多肽部分。SRP的早期募集为扩大底物鉴定窗口提供了一种机制。我们认为，SRP-核糖体相互作用的动力学不仅受到SRP与暴露信号序列的直接结合的影响，还受到隧道内触发的翻译核糖体特性的影响。
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.