A two-step recognition of signal sequences determines the translocation efficiency of proteins
A two-step recognition of signal sequences determines the translocation efficiency of proteins
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DOI：
10.1002/j.1460-2075.1996.tb00379.x
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发表时间：
1996-02-01
期刊：
影响因子：
11.4
通讯作者：
Strub, K
中科院分区：
文献类型：
--
作者：
Belin, D;Bost, S;Strub, K
纤溶酶原激活物抑制剂-2（派-2）的胞质和分泌的N-糖基化形式是通过兼性易位产生的。为了研究导致蛋白质双拓扑分布的分子事件，我们在体外测定了几种信号序列在靶向过程中结合信号识别颗粒（SRP）的能力，以及促进小鼠派-2（mPAI-2）的载体转运的能力。有趣的是，我们比较的六个信号序列例如，mPAI-2信号序列首先以中等效率结合SRP，其次促进仅一部分SRP结合的新生链的载体转运，我们的研究结果提供了证据，证明蛋白质的易位效率可以通过识别其信号序列在两个步骤中进行控制：在SRP介导的靶向期间和在形成定向易位复合物期间，该第二识别可以在插入/易位步骤期间的几个时间点发生。总之，信号序列具有比先前预期的更复杂的结构，允许与易位机制的多重和独立的相互作用。
The cytosolic and secreted, N-glycosylated, forms of plasminogen activator inhibitor-2 (PAI-2) are generated by facultative translocation, To study the molecular events that result in the bi-topological distribution of proteins, we determined in vitro the capacities of several signal sequences to bind the signal recognition particle (SRP) during targeting, and to promote vectorial transport of murine PAI-2 (mPAI-2), Interestingly, the six signal sequences we compared (mPAI-2 and three mutated derivatives thereof, ovalbumin and preprolactin) were found to have differential activities in the two events, For example, the mPAI-2 signal sequence first binds SRP with moderate efficiency and secondly promotes the vectorial transport of only a fraction of the SRP-bound nascent chains, Our results provide evidence that the translocation efficiency of proteins can be controlled by the recognition of their signal sequences at two steps: during SRP-mediated targeting and during formation of a committed translocation complex, This second recognition may occur at several time points during the insertion/translocation step. In conclusion, signal sequences have a more complex structure than previously anticipated, allowing for multiple and independent interactions with the translocation machinery.