Dynamic association of trigger factor with protein substrates
Dynamic association of trigger factor with protein substrates
复制标题
DOI：
10.1006/jmbi.2000.5192
复制
发表时间：
2001-12-14
影响因子：
5.6
通讯作者：
Schmid, FX
中科院分区：
文献类型：
--
作者：
Maier, R;Scholz, C;Schmid, FX
触发因子是一种核糖体结合的折叠辅助因子，显然它结合了两种功能：新生蛋白质的陪伴和折叠过程中催化脯氨酰异构化。核糖体上的直接伴侣结合可能会干扰快速的蛋白质折叠反应，我们发现触发因子确实延迟了具有天然脯氨酰异构体的蛋白质的体外折叠。触发因子与重折叠蛋白结合的动力学分析表明，触发因子对构象折叠的不利影响通过快速结合和释放而最小化。因此，触发因子和底物蛋白之间的复合物的寿命非常短，快速折叠蛋白可以有效地避免与触发因子的意外相互作用。具有不正确脯氨酰异构体的蛋白质链无法完成折叠，因此可以重新结合以进行进一步的催化。与 DnaK 不同，触发因子在不依赖于核苷酸的结合反应中与底物蛋白相互作用，该反应似乎针对高催化活性而不是伴侣功能进行了优化。当 DnaK 和触发因子的基因都被破坏时观察到的合成致死率可能是间接连锁所致。在缺乏触发因子的情况下，折叠会被延迟，并且会形成更多的聚集体，而当 DnaK 缺乏时，也无法预防或处理这些聚集体。 (C) 2001 年学术出版社。
Trigger factor is a ribosome-bound folding helper, which, apparently, combines two functions, chaperoning of nascent proteins and catalyzing prolyl isomerization in their folding. Immediate chaperone binding at the ribosome might interfere with rapid protein folding reactions, and we find that trigger factor indeed retards the in vitro folding of a protein with native prolyl isomers. The kinetic analysis of trigger factor binding to a refolding protein reveals that the adverse effects of trigger factor on conformational folding are minimized by rapid binding and release. The complex between trigger factor and a substrate protein is thus very short-lived, and fast-folding proteins can escape efficiently from an accidental interaction with trigger factor. Protein chains with incorrect prolyl isomers cannot complete folding and therefore can rebind for further rounds of catalysis. Unlike DnaK, trigger factor interacts with substrate proteins in a nucleotide-independent binding reaction, which seems to be optimized for high catalytic activity rather than for chaperone function. The synthetic lethality, observed when the genes for both DnaK and trigger factor are disrupted, might result from an indirect linkage. In the absence of trigger factor, folding is retarded and more aggregates form, which can neither be prevented nor disposed of when DnaK is lacking as well. (C) 2001 Academic Press.