CATALYSIS OF PROTEIN FOLDING BY PROLYL ISOMERASE
CATALYSIS OF PROTEIN FOLDING BY PROLYL ISOMERASE
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DOI：
10.1038/329268a0
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发表时间：
1987-09-17
期刊：
影响因子：
64.8
通讯作者：
FISCHER, G
中科院分区：
文献类型：
--
作者：
LANG, K;SCHMID, FX;FISCHER, G
蛋白质折叠反应的速率变化很大。一些变性的蛋白质在几毫秒或几秒钟内就能恢复原来的构象，而另一些则在几分钟或几小时的时间内非常缓慢地重新折叠。不同的折叠率不仅可以观察到不同的蛋白质，而且可以检测到单个多肽物种。这源于未折叠蛋白的快折叠和慢折叠形式共存，它们以不同的速率恢复原始状态1 - 4。脯氨酸假说为这种异质性提供了一个合理的解释。它假设慢折叠分子具有脯氨酸和另一残基之间的肽键的非天然异构体，并且慢折叠分子的重折叠的关键步骤受到这种不正确的脯氨酸肽键缓慢再异构化的速度限制5 - 9。近年来，从猪肾中发现并纯化了肽基脯氨酸-反异构酶（PPIase）。它能有效地催化脯氨酸酰亚胺肽键在低聚肽10,11中的<s:1>反异构化反应。在这里，我们表明它也催化了一些蛋白质的缓慢的重折叠步骤，这些蛋白质的快速和慢折叠物种已经被观察到，并表明脯氨酸异构化参与了缓慢的重折叠。催化的效率取决于在重折叠蛋白质链中特定的脯氨酸肽键的异构酶的可及性。
Rates of protein folding reactions vary considerably. Some denatured proteins regain the native conformation within milliseconds or seconds, whereas others refold very slowly in the time range of minutes or hours. Varying folding rates are observed not only for different proteins, but can also be detected for single polypeptide species. This originates from the co-existence of fast-and slow-folding forms of the unfolded protein, which regain the native state with different rates1–4. The proline hypothesis provides a plausible explanation for this heterogeneity. It assumes that the slow-folding molecules possess non-native isomers of peptide bonds between proline and another residue, and that crucial steps in the refolding of the slow-folding molecules are limited in rate by the slow reisomerization of such incorrect proline peptide bonds5–9. Recently the enzyme peptidyl-prolylcis-transisomerase (PPIase) was discovered and purified from pig kidney. It catalyses efficiently thecis↽transisomerization of proline imidic peptide bonds in oligopeptides10,11. Here we show that it also catalyses slow steps in the refolding of a number of proteins of which fast- and slow-folding species have been observed and where it was suggested that proline isomerization was involved in slow refolding. The efficiency of catalysis depends on the accessibility for the isomerase of the particular proline peptide bonds in the refolding protein chain.