Nascent Polypeptide Domain Topology and Elongation Rate Direct the Cotranslational Hierarchy of Hsp70 and TRiC/CCT.
Nascent Polypeptide Domain Topology and Elongation Rate Direct the Cotranslational Hierarchy of Hsp70 and TRiC/CCT.
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DOI：
10.1016/j.molcel.2019.06.036
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发表时间：
2019-09
期刊：
影响因子：
16
通讯作者：
K. Stein;Allison Kriel;J. Frydman
中科院分区：
文献类型：
--
作者：
K. Stein;Allison Kriel;J. Frydman
共翻译蛋白质折叠需要精细的核糖体相关分子伴侣网络的帮助。目前尚不清楚生长中的新生多肽中不断变化的信息如何决定功能不同的伴侣的招募。在这里，我们使用核糖体分析，以确定原则的伴侣TRiC/CCT和Hsp 70/Ssb的共翻译行动。我们表明，这些分子伴侣被顺序招募到特定的网站内选择新生多肽的结构域编码区。热休克蛋白70协会第一，结合整个域的选择位点，而TRiC协会后，出现几乎完整的域，暴露一个未受保护的疏水表面。这表明新生折叠中间体的瞬时拓扑性质驱动连续的伴侣缔合。此外，TRiC和Hsp 70的共翻译募集与翻译延长减慢相关。我们建议，新生的链结构景观的时间调制与当地的延伸率协调，以调节热休克蛋白70和TRiC的共翻译折叠的分层行动。
Cotranslational protein folding requires assistance from elaborate ribosome-associated chaperone networks. It remains unclear how the changing information in a growing nascent polypeptide dictates the recruitment of functionally distinct chaperones. Here, we used ribosome profiling to define the principles governing the cotranslational action of the chaperones TRiC/CCT and Hsp70/Ssb. We show that these chaperones are sequentially recruited to specific sites within domain-encoding regions of select nascent polypeptides. Hsp70 associates first, binding select sites throughout domains, whereas TRiC associates later, upon the emergence of nearly complete domains that expose an unprotected hydrophobic surface. This suggests that transient topological properties of nascent folding intermediates drive sequential chaperone association. Moreover, cotranslational recruitment of both TRiC and Hsp70 correlated with translation elongation slowdowns. We propose that the temporal modulation of the nascent chain structural landscape is coordinated with local elongation rates to regulate the hierarchical action of Hsp70 and TRiC for cotranslational folding.