Native proteins trap high-energy transit conformations.
Native proteins trap high-energy transit conformations.
复制标题
天然蛋白质捕获高能转运构象。
DOI：
10.1126/sciadv.1501188
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发表时间：
2015
期刊：
影响因子：
13.6
通讯作者：
Karplus,PAndrew
中科院分区：
文献类型：
--
作者：
Brereton,AndrewE;Karplus,PAndrew
在蛋白质折叠过程中，作为调节蛋白质功能的一些构象变化的一部分，多肽链必须穿过将通常采用的低能构象分开的高能屏障。肽几何形状的扭曲如何允许这些跨越势垒的转变是一个基本的开放问题。一个这样的重要转变涉及非甘氨酸残基在拉马钱德兰图的左侧（即，λ < 0°）和右侧（即，λ> 0°）之间的移动。我们报告说，通常预期仅作为短暂过渡态发生的具有π ~ 0°的高能构象被稳定地捕获在某些高分辨率的天然蛋白质结构中，并且对这些残基的分析提供了详细的，实验得出的键角扭曲的地图发生沿着过渡路径。这一意外的信息奠定了休息任何不确定性，这种过渡是否是可能的，它们是如何发生的，这样做为理论研究奠定了坚实的基础，以更好地了解盆地之间的过渡，这些盆地很少被研究，但与蛋白质折叠和功能密切相关。此外，一个这样的残基的上下文表明，即使是设计的高度稳定的蛋白质也可能具有实质性的不利相互作用。
During protein folding and as part of some conformational changes that regulate protein function, the polypeptide chain must traverse high-energy barriers that separate the commonly adopted low-energy conformations. How distortions in peptide geometry allow these barrier-crossing transitions is a fundamental open question. One such important transition involves the movement of a non-glycine residue between the left side of the Ramachandran plot (that is, ϕ < 0°) and the right side (that is, ϕ > 0°). We report that high-energy conformations with ϕ ~ 0°, normally expected to occur only as fleeting transition states, are stably trapped in certain highly resolved native protein structures and that an analysis of these residues provides a detailed, experimentally derived map of the bond angle distortions taking place along the transition path. This unanticipated information lays to rest any uncertainty about whether such transitions are possible and how they occur, and in doing so lays a firm foundation for theoretical studies to better understand the transitions between basins that have been little studied but are integrally involved in protein folding and function. Also, the context of one such residue shows that even a designed highly stable protein can harbor substantial unfavorable interactions.