A structural ensemble of a ribosome-nascent chain complex during cotranslational protein folding.
A structural ensemble of a ribosome-nascent chain complex during cotranslational protein folding.
复制标题
DOI：
10.1038/nsmb.3182
复制
发表时间：
2016-04
影响因子：
16.8
通讯作者：
Christodoulou J
中科院分区：
文献类型：
--
作者：
Cabrita LD;Cassaignau AME;Launay HMM;Waudby CA;Wlodarski T;Camilloni C;Karyadi ME;Robertson AL;Wang X;Wentink AS;Goodsell L;Woolhead CA;Vendruscolo M;Dobson CM;Christodoulou J
虽然核糖体结构的详细图片正在出现，但在原子水平上对新生多肽链的结构和共翻译折叠特性知之甚少。在这里，我们已经使用溶液态核磁共振光谱，以确定在生物合成过程中形成的核糖体新生链复合物（RNC）在E。coli中，其中一对免疫球蛋白样结构域采用折叠的N-末端结构域（FLN 5）和无序但紧凑的C-末端结构域（FLN 6）。为了研究FLN 5如何协同获得其天然结构，我们逐步缩短了RNC结构。我们发现，核糖体调节折叠过程，因为FLN 5的完整序列在获得天然结构之前远远超出隧道，而在隔离状态下，即使截短，它也会自发折叠。这一发现表明，在生物合成过程中调节结构获取可以降低错误折叠的可能性，特别是同源结构域。
While detailed pictures are emerging of the structures of ribosomes, little is known at the atomic level about the structural and co-translational folding properties of nascent polypeptide chains. Here we have used solution-state NMR spectroscopy to define a structural ensemble of a ribosome-nascent chain complex (RNC) formed during biosynthesis in E. coli, where a pair of immunoglobulin-like domains adopts a folded N-terminal domain (FLN5) and a disordered but compact C-terminal domain (FLN6). To study how FLN5 acquires its native structure co-translationally, we progressively shortened the RNC constructs. We find that the ribosome modulates the folding process, as the complete sequence of FLN5 emerges well beyond the tunnel before acquiring native structure, while in isolation it folds spontaneously, even when truncated. This finding suggests that regulating structure acquisition during biosynthesis can reduce the probability of misfolding, particularly of homologous domains.