Arrestins: structural disorder creates rich functionality.
Arrestins: structural disorder creates rich functionality.
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DOI：
10.1007/s13238-017-0501-8
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发表时间：
2018-12
期刊：
影响因子：
21.1
通讯作者：
Uversky VN
中科院分区：
文献类型：
--
作者：
Gurevich VV;Gurevich EV;Uversky VN
抑制蛋白是可溶性相对小的44-46 kDa蛋白质，其特异性结合数百个活性磷酸化GPCR和数十个非受体伴侣。有结合伴侣，表现出偏好的每一个已知的抑制蛋白构象：自由，受体结合，和微管结合。最近的证据表明，每种功能状态下的构象灵活性是抑制蛋白的定义特征。蛋白质的柔性或可塑性通常被描述为结构紊乱，与高分辨率晶体结构中观察到的固定构象顺序相反。然而，蛋白质-蛋白质相互作用通常涉及高度柔性的元件，这些元件在与不同的伴侣结合时可以呈现许多不同的构象。现有的证据表明，抑制蛋白也不例外：它们的灵活性是功能多样性所必需的。关于抑制蛋白和许多其他多功能蛋白质的数据表明，在许多情况下，“有序”可能是由高度非生理结晶条件和/或晶体堆积力人为施加的。相比之下，构象灵活性（及其极端情况，内在无序）是蛋白质的一种更自然的状态，代表了作为其生理相关功能基础的真正生物学秩序。
Arrestins are soluble relatively small 44–46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures. However, protein-protein interactions often involve highly flexible elements that can assume many distinct conformations upon binding to different partners. Existing evidence suggests that arrestins are no exception to this rule: their flexibility is necessary for functional versatility. The data on arrestins and many other multi-functional proteins indicate that in many cases, “order” might be artificially imposed by highly non-physiological crystallization conditions and/or crystal packing forces. In contrast, conformational flexibility (and its extreme case, intrinsic disorder) is a more natural state of proteins, representing true biological order that underlies their physiologically relevant functions.
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