Process of biosynthetic protein folding determines the rapid formation of native structure
Process of biosynthetic protein folding determines the rapid formation of native structure
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DOI：
10.1006/jmbi.1999.3281
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发表时间：
1999-11-26
影响因子：
5.6
通讯作者：
Baldwin, TO
中科院分区：
文献类型：
--
作者：
Fedorov, AN;Baldwin, TO
生物合成折叠是所有蛋白质的共同功能，从不断增长的新生链条开始，并在其适当的细胞环境中导致生物活性结构。我们发现细菌荧光素酶β亚基在生物合成折叠过程中比在尿素重折叠过程中更快地达到其在αβ异源二聚体中的最终天然形式。活性酶的形成速度是由一种短暂的折叠中间体决定的，这种折叠中间体从核糖体释放后能够非常迅速地与阿尔法亚基结合。这种中间体似乎涉及β亚基的C-末端区域的瞬时相互作用，该区域远离亚基界面，但密切参与异源二聚化。在类似条件下，β亚基的重折叠速度要慢得多。我们已经表征了这两条途径，并表明生物合成折叠和尿素复性之间的基本区别是，新合成的β亚基在慢速决定步骤之后进入折叠途径，该步骤限制了复性过程的速度，并构成了动力学陷阱。这一机制体现了一种主要的策略，即避免缓慢折叠的中间产物和动力学陷阱，许多蛋白质可能利用这一策略来实现快速有效的生物合成折叠。(C)1999年学术出版社。
Biosynthetic folding, beginning with the growing nascent chain and leading to the biologically active structure within its proper cellular context, is one function shared by all proteins. We show that the bacterial luciferase beta subunit reaches its final native form in the alpha beta heterodimer much more rapidly during biosynthetic folding than during refolding from urea. The rate of formation of active enzyme is determined by a short-lived folding intermediate, which is able to associate with the alpha subunit very rapidly following release from the ribosome. This intermediate appears to involve a transient interaction of the C-terminal region of the beta subunit, a region distant from the subunit interface, but intimately involved in heterodimerization. Refolding of the beta subunit under similar conditions proceeds much more slowly. We have characterized both pathways and show that the basic difference between biosynthetic folding and refolding from urea is that the newly synthesized beta subunit enters the folding pathway at a point beyond the slow, rate-determining step that limits the rate of the renaturation process and constitutes a kinetic trap. This mechanism embodies a major strategy, the avoidance of slow-folding intermediates and kinetic traps, that may be employed by many proteins to achieve fast and efficient biosynthetic folding. (C) 1999 Academic Press.