Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
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DOI：
10.1038/s41598-019-44928-3
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发表时间：
2019-06-10
影响因子：
4.6
通讯作者：
Trovato, Antonio
中科院分区：
文献类型：
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作者：
Baiesi, Marco;Orlandini, Enzo;Trovato, Antonio
蛋白质必须快速折叠，才能获得具有生物功能的三维天然结构。因此，这些主要是通过局部接触来稳定的，而像打结这样的复杂拓扑很少见。在这里，我们揭示了蛋白质序列和结构处理骨干自纠缠所采用的特定模式的存在。对蛋白质数据库的大规模分析表明，与另一个链部分显著交织的环通常被弱结合的氨基酸闭合。为什么这种精力充沛的挫折感会持续下去？一种可能的情况是，只有在折叠过程接近尾声时才形成纠缠环，以避免动力学陷阱。一致地，这些环更频繁地被发现缠绕在其N-末端一侧的链的一部分，即较早在核糖体上翻译的那条链。最后，这些基序在自然状态下没有在模拟的类蛋白质结构中那么丰富，但它们出现在32%的蛋白质中，在某些情况下，它们表现出令人惊讶的复杂交织。
Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement. A large scale analysis of the Protein Data Bank shows that loops significantly intertwined with another chain portion are typically closed by weakly bound amino acids. Why is this energetic frustration maintained? A possible picture is that entangled loops are formed only toward the end of the folding process to avoid kinetic traps. Consistently, these loops are more frequently found to be wrapped around a portion of the chain on their N-terminal side, the one translated earlier at the ribosome. Finally, these motifs are less abundant in natural native states than in simulated protein-like structures, yet they appear in 32% of proteins, which in some cases display an amazingly complex intertwining.