Protein topology determines binding mechanism
Protein topology determines binding mechanism
复制标题
DOI：
10.1073/pnas.2534828100
复制
发表时间：
2004-01-13
影响因子：
11.1
通讯作者：
Onuchic, JN
中科院分区：
文献类型：
--
作者：
Levy, Y;Wolynes, PG;Onuchic, JN
蛋白质的识别和结合可以产生短暂的或长期存在的复合物，在许多生物学功能中起着重要作用，但有时也会导致病理聚集。我们使用一个简化的模拟模型来调查一系列系统，其中两个高度灵活的蛋白质链形成一个同型二聚体。在所有情况下，该模型对应于折叠和结合的完美漏斗能量景观，再现了关于折叠和结合是否在一步中耦合或是否发生中间产物的宏观实验观察。由于最小挫折原则，我们发现，在蛋白质折叠的情况下，原生拓扑结构是决定结合机制选择的主要因素。即使单体本身是稳定的，有时通过未折叠的中间体进行结合也是最快的，因此显示了在分子识别的“飞铸”场景中所设想的加速。
Protein recognition and binding, which result in either transient or long-lived complexes, play a fundamental role in many biological functions, but sometimes also result in pathologic aggregates. We use a simplified simulation model to survey a range of systems where two highly flexible protein chains form a homodimer. In all cases, this model, which corresponds to a perfectly funneled energy landscape for folding and binding, reproduces the macroscopic experimental observations on whether folding and binding are coupled in one step or whether intermediates occur. Owing to the minimal frustration principle, we find that, as in the case of protein folding, the native topology is the major factor that governs the choice of binding mechanism. Even when the monomer is stable on its own, binding sometimes occurs fastest through unfolded intermediates, thus showing the speedup envisioned in the fly-casting scenario for molecular recognition.