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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Folding of large multidomain proteins by partial encapsulation in the chaperonin TRiC/CCT
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Folding of large multidomain proteins by partial encapsulation in the chaperonin TRiC/CCT

机译：通过部分包裹在伴侣蛋白TRiC / CCT中折叠大的多域蛋白

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摘要

The eukaryotic chaperonin, TRiC/CCT (TRiC, TCP-1 ring complex; CCT, chaperonin containing TCP-1), uses a built-in lid to mediate protein folding in an enclosed central cavity. Recent structural data suggest an effective size limit for the TRiC folding chamber of ～70 kDa, but numerous chaperonin substrates are substantially larger. Using artificial fusion constructs with actin, an obligate chaperonin substrate, we show that TRiC can mediate folding of large proteins by segmental or domain-wise encapsulation. Single or multiple protein domains up to ～70 kDa are stably enclosed by stabilizing the ATP-hydrolysis transition state of TRiC. Additional domains, connected by flexible linkers that pass through the central opening of the folding chamber, are excluded and remain accessible to externally added protease. Experiments with the physiological TRiC substrate hSnu114, a 109-kDa multidomain protein, suggest that TRiC has the ability to recognize domain boundaries in partially folded intermediates. In the case of hSnu114, this allows the selective encapsulation of the C-terminal ～45-kDa domain and segments thereof, presumably reflecting a stepwise folding mechanism. The capacity of the eukaryotic chaperonin to overcome the size limitation of the folding chamber may have facilitated the explosive expansion of the multidomain proteome in eukaryotes.
机译：真核伴侣蛋白TRiC / CCT（TRiC，TCP-1环复合物； CCT，包含TCP-1的伴侣蛋白），使用内置的盖子来介导蛋白质在封闭的中央腔中折叠。最近的结构数据表明，TRiC折叠室的有效尺寸限制为〜70 kDa，但许多伴侣蛋白底物却大得多。使用人工融合的肌动蛋白，专职的伴侣蛋白底物的融合构建体，我们表明TRiC可以通过分段或域封装来介导大蛋白的折叠。通过稳定TRiC的ATP水解转变态，可以稳定地封闭高达70 kDa的单个或多个蛋白质结构域。通过挠性接头穿过折叠室中心开口的其他结构域被排除在外，使外部添加的蛋白酶仍可接近。使用生理学TRiC底物hSnu114（109-kDa的多结构域蛋白）进行的实验表明，TRiC具有识别部分折叠的中间体中结构域边界的能力。在hSnu114的情况下，这允许C端〜45 kDa结构域及其片段的选择性封装，大概反映了逐步折叠的机制。真核伴侣蛋白克服折叠腔的大小限制的能力可能已经促进了多域蛋白质组在真核生物中的爆炸性扩展。

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