Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains
Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains
复制标题
DOI：
10.1371/journal.pcbi.1000645
复制
发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Smith, Jeremy C.
中科院分区：
文献类型：
--
作者：
Daidone, Isabella;Neuweiler, Hannes;Smith, Jeremy C.
未折叠多肽链中端到端闭环动力学的长度依赖性的表征提供了对蛋白质折叠早期步骤的理解。在这里，通过将单分子荧光光谱与分子动力学模拟相结合来研究聚甘氨酸-丝氨酸肽的闭环。对于含有超过 10 个肽键的链，20-100 纳秒时间范围内的闭环速率常数表现出幂律长度依赖性。然而，对于较短的肽，这种缩放会分解，由于实验设置中使用的染料报告系统引起的扰动，较短的肽表现出较慢的动力学。发现较长肽中的闭环动力学是由肽内氢键和瞬时β-折叠结构的形成决定的，相对于不能形成氢键的多肽链的情况，这加速了对序列较远的残基之间接触的搜索。这里发现的生理条件下未折叠肽中氢键驱动的多肽链折叠不仅与蛋白质折叠的分层模型一致，这凸显了折叠过程早期二级结构形成的重要性，而且还被证明可以加快对有效折叠事件的搜索。
Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20-100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient beta-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events.