MTA-DE Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
J Mol Biol. 2018 Aug 3;430(16):2278-2287. doi: 10.1016/j.jmb.2018.02.015. Epub 2018 Feb 23.
The proposal that coupled folding to binding is not an obligatory mechanism for intrinsically disordered (ID) proteins was put forward 10 years ago. The notion of fuzziness implies that conformational heterogeneity can be maintained upon interactions of ID proteins, which has a functional impact either on regulated assembly or activity of the corresponding complexes. Here I review how the concept has evolved in the past decade, via increasing experimental data providing insights into the mechanisms, pathways and regulatory modes. The effects of structural diversity and transient contacts on protein assemblies have been collected and systematically analyzed (Fuzzy Complexes Database, http://protdyn-database.org). Fuzziness has also been exploited as a framework to decipher molecular organization of higher-order protein structures. Quantification of conformational heterogeneity opens exciting future perspectives for drug discovery from small molecule-ID protein interactions to supramolecular assemblies.
10 年前就有人提出，折叠与结合偶联并不是无序蛋白（ID）的必需机制。模糊性概念意味着 ID 蛋白相互作用时可以维持构象异质性，这对相应复合物的调节组装或活性有功能影响。本文通过越来越多的实验数据深入了解机制、途径和调控模式，回顾了该概念在过去十年中的发展。已收集并系统分析了结构多样性和瞬时接触对蛋白质组装的影响（模糊复合物数据库，http://protdyn-database.org）。模糊性也被用作框架来解析高级别蛋白质结构的分子组织。构象异质性的定量为从小分子-ID 蛋白相互作用到超分子组装的药物发现开辟了令人兴奋的未来前景。
