Department of chemistry, Brandeis University, 415 South St, Waltham, MA, 02454, USA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Angew Chem Int Ed Engl. 2017 Jun 19;56(26):7579-7583. doi: 10.1002/anie.201702783. Epub 2017 May 24.
Based on the recent near-atomic structures of the PYRIN domain of ASC in the protein filament of inflammasomes and the observation that the active form of vitamin B6 (pyridoxal phosphate, P5P) modulates the self-assembly of ASC, we rationally designed an N-terminal capped nonapeptide (Nap-FFKKFKLKL, 1) to form supramolecular nanofibers consisting of α-helix. The addition of P5P to the solution of 1 results in a hydrogel almost instantly (about 4 seconds). Several other endogenous small molecules (for example, pyridoxal, folinic acid, ATP, and AMP) also convert the solution of 1 into a hydrogel. As the demonstration of correlating assemblies of peptides and the relevant protein epitopes, this work illustrates a bioinspired approach to develop supramolecular structures modulated by endogenous small molecules.
基于 ASC 的吡喃酮域在炎症小体蛋白丝中的最近的近原子结构,以及观察到维生素 B6 的活性形式(磷酸吡哆醛,P5P)调节 ASC 的自组装,我们合理设计了一个 N-端封端的九肽(Nap-FFKKFKLKL,1)以形成由α-螺旋组成的超分子纳米纤维。将 P5P 添加到 1 的溶液中会几乎立即(约 4 秒)形成水凝胶。其他几种内源性小分子(例如,吡哆醛、叶酸、ATP 和 AMP)也会将 1 的溶液转化为水凝胶。作为肽和相关蛋白表位的组装相关性的证明,这项工作说明了一种受内源性小分子调节的超分子结构的仿生方法。