Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding
Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding
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DOI：
10.1038/nsmb.2615
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发表时间：
2013-07-01
影响因子：
16.8
通讯作者：
Kramer, Guenter
中科院分区：
文献类型：
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作者：
Sandikci, Arzu;Gloge, Felix;Kramer, Guenter
新合成的多肽经历各种共翻译成熟步骤，包括N-末端酶促加工，分子伴侣辅助折叠和膜靶向，但这些步骤的空间和时间协调尚不清楚。我们发现，大肠杆菌甲硫氨酸氨肽酶（MAP）与核糖体通过一个带电的环，这是至关重要的新生链加工和细胞活力。MAP与肽脱甲酰基酶（PDF）竞争核糖体隧道出口处的结合位点，肽脱甲酰基酶是第一种作用于新生链的酶。PDF具有极快的缔合和解离动力学，这使得它能够频繁地对核糖体进行采样，并确保在新生链出现后对其进行处理。伴侣触发因子的过早募集或多肽折叠对加工效率产生负面影响。因此，PDF和MAP的快速核糖体缔合动力学对于初生链加工与后期成熟事件（包括伴侣蛋白募集和折叠）的时间分离至关重要。
Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates with ribosomes through a charged loop that is crucial for nascent-chain processing and cell viability. MAP competes with peptide deformylase (PDF), the first enzyme to act on nascent chains, for binding sites at the ribosomal tunnel exit. PDF has extremely fast association and dissociation kinetics, which allows it to frequently sample ribosomes and ensure the processing of nascent chains after their emergence. Premature recruitment of the chaperone trigger factor, or polypeptide folding, negatively affect processing efficiency. Thus, the fast ribosome association kinetics of PDF and MAP are crucial for the temporal separation of nascent-chain processing from later maturation events, including chaperone recruitment and folding.