Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins
Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins
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DOI：
10.1038/nature02899
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发表时间：
2004-09-30
期刊：
影响因子：
64.8
通讯作者：
Ban, N
中科院分区：
文献类型：
--
作者：
Ferbitz, L;Maier, T;Ban, N
在蛋白质生物合成过程中，从核糖体出口通道出现的新生多肽链遇到核糖体相关的分子伴侣，这有助于它们折叠成天然状态（1，2）。在这里，我们提出了一个2.7埃的晶体结构的大肠杆菌触发因子，这种类型的最好的特征分子伴侣，连同它的核糖体结合结构域的复杂性与海盐蚌大核糖体亚基。触发因子采用类似于蹲伏的龙的独特构象，具有形成氨基末端核糖体结合“尾”、肽基脯氨酰异构酶“头”、羧基末端“臂”和建立“背”的连接区域的分离结构域。从其在核糖体上的附着点，触发因子将延伸的结构域投射到核糖体隧道的出口上，产生受保护的折叠空间，在该折叠空间中新生多肽可以被保护免受蛋白酶和聚集的影响。这项研究为我们理解共翻译蛋白质折叠提供了新的思路，并提出了核糖体相关分子伴侣的一种意想不到的作用机制。
During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosome-associated chaperones, which assist their folding to the native state(1,2). Here we present a 2.7 Angstrom crystal structure of Escherichia coli trigger factor, the best-characterized chaperone of this type, together with the structure of its ribosome-binding domain in complex with the Haloarcula marismortui large ribosomal subunit. Trigger factor adopts a unique conformation resembling a crouching dragon with separated domains forming the amino-terminal ribosome-binding 'tail', the peptidylprolyl isomerase 'head', the carboxy-terminal 'arms' and connecting regions building up the 'back'. From its attachment point on the ribosome, trigger factor projects the extended domains over the exit of the ribosomal tunnel, creating a protected folding space where nascent polypeptides may be shielded from proteases and aggregation. This study sheds new light on our understanding of co-translational protein folding, and suggests an unexpected mechanism of action for ribosome-associated chaperones.