Multiple routes lead to the native state in the energy landscape of the β-trefoil family
Multiple routes lead to the native state in the energy landscape of the β-trefoil family
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DOI：
10.1073/pnas.0510110103
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发表时间：
2006-07-05
影响因子：
11.1
通讯作者：
Onuchic, Jose N.
中科院分区：
文献类型：
--
作者：
Chavez, Leslie L.;Gosavi, Shachi;Onuchic, Jose N.
一般来说，真实蛋白质的能量景观设计得足够好，局部能量最小值的深度与本地状态的全局偏差相比是小的。由于能量景观的漏斗性质，缺乏能量挫折的模型已经能够捕捉到在小蛋白质和大蛋白质的实验研究中发现的过渡态和中间产物的主要结构特征。在这项研究中，我们的问题是：由于局部拓扑约束偏离第三纪褶皱，特定结构家族成员之间折叠机制的实验差异是否与家族共同？选择β -三叶结构家族成员IL-1 β， hisactophilin和酸性/碱性fgf来解决这个问题。已经观察到，β -三叶草的拓扑景观允许不同的种群，几何上不相连的路线，为这个家族提供能量相似但结构不同的折叠方式。拓扑结构或能量学的微小变化可以改变首选路线。综上所述，这些结果表明β -三叶草家族的整体折叠决定了能量景观，但在该景观上获取的路线可能因个体家族成员的功能需求而有所不同。
In general, the energy landscapes of real proteins are sufficiently well designed that the depths of local energetic minima are small compared with the global bias of the native state. Because of the funneled nature of energy landscapes, models that lack energetic frustration have been able to capture the main structural features of the transition states and intermediates found in experimental studies of both small and large proteins. In this study we ask: Are the experimental differences in folding mechanisms among members of a particular structural family due to local topological constraints that deviate from the tertiary fold common to the family? The beta-trefoil structural family members IL-1 beta, hisactophilin, and acidic/basic FGFs were chosen to address this question. It has been observed that the topological landscape of the beta-trefoils allows for the population of diverse, geometrically disconnected routes that provide energetically similar but structurally distinct ways for this family to fold. Small changes in topology or energetics can alter the preferred route. Taken together, these results indicate that the global fold of the beta-trefoil family determines the energy landscape but that the routes accessed on that landscape might differ as a result of functional requirements of the individual family members.