Making and Breaking Supramolecular Synthons for Modular Protein Frameworks.

IF 3.9 2区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Niamh Mockler, Colin Raston, Peter B Crowley
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Abstract

Anionic calixarenes are useful mediators of protein assembly. In some cases, protein - calixarene cocrystallization yields multiple polymorphs. Ralstonia solanacearum lectin (RSL) cocrystallizes with p-sulfonato-calix[8]arene (sclx8) in at least four distinct pH-dependent arrangements. One of these polymorphs, occurring at pH ≤4, is a cubic framework in which RSL nodes are connected by sclx8 dimers. These dimers are supramolecular synthons, occurring in distinct crystal structures. Now, we show that the discus-shaped dimer of p-phosphonato-calix[6]arene (pclx6), can replace the sclx8 dimer yielding a new assembly of RSL. Remarkably, just one type of RSL - pclx6 cocrystal was formed, irrespective of pH or crystallization condition. These results with pclx6 contrast starkly with sclx8 and suggest that the calixarene type (e.g. phosphonate versus sulfonate) dictates the synthon durability, which in turn exerts control over protein assembly and polymorph selection. Breaking the pclx6 dimer required a mutant of RSL with an affinity tag for macrocycle binding. This highly accessible, dicationic site resulted in a significantly altered and porous framework with pclx6 (but not with sclx8). Experiments with ternary mixtures of RSL, pclx6 and sclx8 provide evidence of pH-driven self-sorting. Thus, the 'mix-and-match' of protein and supramolecular synthons is a promising approach to protein crystal engineering.

构建和破坏模块化蛋白质框架的超分子合成子。
阴离子杯芳烃是有用的蛋白质组装介质。在某些情况下,蛋白质-杯芳烃共结晶产生多种多态性。龙葵凝集素(RSL)与对磺酰基杯芳烃(sclx8)共结晶,至少有四种不同的ph依赖性排列。其中一种在pH≤4时发生的多态性是一个立方框架,其中RSL节点由sclx8二聚体连接。这些二聚体是超分子合子,以不同的晶体结构出现。现在,我们证明了对膦杯[6]芳烃的铁饼状二聚体(pclx6)可以取代sclx8二聚体,产生新的RSL组装体。值得注意的是,无论pH值或结晶条件如何,只形成了一种RSL - pclx6共晶。pclx6的这些结果与sclx8形成鲜明对比,表明杯芳烃类型(如膦酸盐与磺酸盐)决定了合成子的耐久性,这反过来又控制了蛋白质组装和多态性选择。破坏pclx6二聚体需要一个带有大环结合亲和标签的RSL突变体。这个高度可访问的、指示式的站点导致pclx6(而不是sclx8)的框架发生了显著的变化和多孔性。用RSL、pclx6和sclx8的三元混合物进行的实验提供了ph驱动的自分选的证据。因此,蛋白质和超分子合成子的“混合匹配”是一种很有前途的蛋白质晶体工程方法。
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来源期刊
Chemistry - A European Journal
Chemistry - A European Journal 化学-化学综合
CiteScore
7.90
自引率
4.70%
发文量
1808
审稿时长
1.8 months
期刊介绍: Chemistry—A European Journal is a truly international journal with top quality contributions (2018 ISI Impact Factor: 5.16). It publishes a wide range of outstanding Reviews, Minireviews, Concepts, Full Papers, and Communications from all areas of chemistry and related fields. Based in Europe Chemistry—A European Journal provides an excellent platform for increasing the visibility of European chemistry as well as for featuring the best research from authors from around the world. All manuscripts are peer-reviewed, and electronic processing ensures accurate reproduction of text and data, plus short publication times. The Concepts section provides nonspecialist readers with a useful conceptual guide to unfamiliar areas and experts with new angles on familiar problems. Chemistry—A European Journal is published on behalf of ChemPubSoc Europe, a group of 16 national chemical societies from within Europe, and supported by the Asian Chemical Editorial Societies. The ChemPubSoc Europe family comprises: Angewandte Chemie, Chemistry—A European Journal, European Journal of Organic Chemistry, European Journal of Inorganic Chemistry, ChemPhysChem, ChemBioChem, ChemMedChem, ChemCatChem, ChemSusChem, ChemPlusChem, ChemElectroChem, and ChemistryOpen.
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