Extreme Fuzziness: Direct Interactions between Two IDPs
Extreme Fuzziness: Direct Interactions between Two IDPs
复制标题
极度模糊：两个国内流离失所者之间的直接互动
DOI：
10.3390/biom9030081
复制
发表时间：
2019-02
期刊：
影响因子：
5.5
通讯作者：
Wang Dongdong
中科院分区：
文献类型：
--
作者：
Wang Wenning;Wang Dongdong
涉及内在无序蛋白（IDP）的蛋白质相互作用极大地扩展了蛋白质可用的结合机制的范围。在采用耦合折叠和结合的相互作用中，IDP经历无序到有序的转变以形成具有明确结构的复合物。在许多其他情况下，IDP在最终的复合物中保留了结构可塑性，这被定义为模糊复合物。虽然大量的模糊复合物已被表征为具有各种模糊模式，但许多相互作用是在IDP和结构化蛋白质之间。因此，两个IDP是否可以直接相互作用，形成一个模糊的复杂的无序到有序的过渡仍然是一个悬而未决的问题。近年来，两项关于IDPs相互作用的研究（4.1G-CTD/NuMA和H1/ProTα）为这一问题找到了明确的答案。详细的表征结合核磁共振（NMR），单分子Förster共振能量转移（smFRET）和分子动力学（MD）模拟表明，这两对IDP之间的直接相互作用确实形成模糊复合物，同时保留了分离蛋白质的构象动力学，我们称之为极端模糊复合物。极端future完成了蛋白质-蛋白质相互作用模式的全谱，这表明需要一个超越现有结合机制的更通用的模型。以前的蛋白质相互作用模型可以适用于极端模糊相互作用的某些方面，但在更普遍的意义上，天然和非天然接触之间的区别，这是用来理解蛋白质折叠和结合，变得模糊。探索极端荧光现象可能为分子识别和药物设计提供新的思路。
Protein interactions involving intrinsically disordered proteins (IDPs) greatly extend the range of binding mechanisms available to proteins. In interactions employing coupled folding and binding, IDPs undergo disorder-to-order transitions to form a complex with a well-defined structure. In many other cases, IDPs retain structural plasticity in the final complexes, which have been defined as the fuzzy complexes. While a large number of fuzzy complexes have been characterized with variety of fuzzy patterns, many of the interactions are between an IDP and a structured protein. Thus, whether two IDPs can interact directly to form a fuzzy complex without disorder-to-order transition remains an open question. Recently, two studies of interactions between IDPs (4.1G-CTD/NuMA and H1/ProTα) have found a definite answer to this question. Detailed characterizations combined with nuclear magnetic resonance (NMR), single-molecule Förster resonance energy transfer (smFRET) and molecular dynamics (MD) simulation demonstrate that direct interactions between these two pairs of IDPs do form fuzzy complexes while retaining the conformational dynamics of the isolated proteins, which we name as the extremely fuzzy complexes. Extreme fuzziness completes the full spectrum of protein-protein interaction modes, suggesting that a more generalized model beyond existing binding mechanisms is required. Previous models of protein interaction could be applicable to some aspects of the extremely fuzzy interactions, but in more general sense, the distinction between native and nonnative contacts, which was used to understand protein folding and binding, becomes obscure. Exploring the phenomenon of extreme fuzziness may shed new light on molecular recognition and drug design.
登录
查看更多内容
影响因子：
6.8
作者：
Zhou HX;Bates PA
通讯作者：
Bates PA
影响因子：
14.9
作者：
Parra RG;Schafer NP;Radusky LG;Tsai MY;Guzovsky AB;Wolynes PG;Ferreiro DU
通讯作者：
Ferreiro DU
影响因子：
6.8
作者：
Chen, Tao;Song, Jianhui;Chan, Hue Sun
通讯作者：
Chan, Hue Sun
影响因子：
64.5
作者：
Tomomi Kiyomitsu;I. Cheeseman
通讯作者：
Tomomi Kiyomitsu;I. Cheeseman
影响因子：
3.4
作者：
Williams JK;Yang X;Baum J
通讯作者：
Baum J