Center for Molecular Biology of the University of Heidelberg, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Mol Cell. 2012 Oct 12;48(1):63-74. doi: 10.1016/j.molcel.2012.07.018. Epub 2012 Aug 23.
How nascent polypeptides emerging from ribosomes fold into functional structures is poorly understood. Here, we monitor disulfide bond formation, protease resistance, and enzymatic activity in nascent polypeptides to show that in close proximity to the ribosome, conformational space and kinetics of folding are restricted. Folding constraints decrease incrementally with distance from the ribosome surface. Upon ribosome binding, the chaperone Trigger Factor counters folding also of longer nascent chains, to extents varying between different chain segments. Trigger Factor even binds and unfolds pre-existing folded structures, the unfolding activity being limited by the thermodynamic stability of nascent chains. Folding retardation and unfolding activities are not shared by the DnaK chaperone assisting later folding steps. These ribosome- and Trigger Factor-specific activities together constitute an efficient mechanism to prevent or even revert premature folding, effectively limiting misfolded intermediates during protein synthesis.
新生多肽从核糖体中折叠成具有功能的结构的方式还不太清楚。在这里，我们监测新生多肽中二硫键的形成、蛋白酶抗性和酶活性，结果表明，在核糖体附近，折叠的构象空间和动力学受到限制。折叠的限制随着与核糖体表面距离的增加而逐渐减少。在核糖体结合后，伴侣蛋白触发因子（Trigger Factor）也会阻碍更长新生链的折叠，其阻碍程度因不同的链段而异。触发因子甚至可以结合和解折叠预先存在的折叠结构，其解折叠活性受到新生链热力学稳定性的限制。折叠延迟和解折叠活性与辅助后续折叠步骤的 DnaK 伴侣蛋白不同。这些核糖体和触发因子特有的活性共同构成了一种有效的机制，可以防止甚至逆转过早折叠，有效地限制蛋白质合成过程中错误折叠的中间体。
