Protein amyloid fibers are one of the important self-assembled forms of proteins, which were first found in the pathological brain tissue of patients with a variety of neurodegenerative diseases, and are regarded as the core pathological markers of a variety of neurodegenerative diseases. In recent years, it has been found that a variety of proteins or peptides can be dynamically assembled to form functional amyloid fibers under physiological conditions, participate in the regulation of biological processes, and exhibit excellent mechanical properties, high environmental stability and self-healing ability, thus becoming a class of functional bionanomaterials with important development potential. Different modification methods of polypeptides can significantly affect the morphology of their self-assembly into amyloid fibers and the characteristics of nanomaterials. In particular, halogenated modification of peptides has been shown to enhance the stability of fiber structures. However, how to realize the self-assembly of atomic-level regulated polypeptides and how to optimize the structure and properties of amyloid fibers by using halogenated modification are still core problems to be solved in this field.
Recently, Liu Cong's research group from the Interdisciplinary Center of Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, and Dai Bin's research group from the Department of Instrument Science and Engineering of Shanghai Jiao Tong University, published a research paper entitled Creating an amyloid 'kaleidoscope' using short iodinated peptides in German Applied Chemistry. This work creates amyloid fiber assemblies with a variety of different atomic structures and physicochemical properties by introducing iodination modifications at different sites of the polypeptide. Based on the in-depth study of structure and assembly mechanism, the team further designed and obtained amyloid iodide fibers with a new polypeptide arrangement. This work provides new ideas and directions for the construction of a "kaleidoscope" of amyloid fibers with different structures and functions by precisely regulating amyloid fiber assembly through post-translational modification.
This study focused on a peptide sequence 1GFGGNDNFG9 (abbreviated as hnRAC1), which plays an important role in the dynamic assembly of cellular stress particles. The study found that hnRAC1 was able to self-assemble into temperature-sensitive, highly reversible amyloid fibers. To explore the structural properties of the fiber, the researchers used cryo-electron microscopy (cryo-EM) to resolve the atomic structure of the hnRAC1 reversible fiber (Figure 1) and reveal the molecular mechanism of its reversible dynamic assembly.
In addition, by introducing iodine atomic modifications at different sites of hnRAC1, it was found that iodide modifications can induce hnRAC1 to form a "kaleidoscope" of amyloid fibers with different atomic structures and thermal stability (Figure 1). Further studies have found that the self-assembly of these peptide amyloid fibers with different structures is driven by various types of halogen bonds formed within and between peptide molecules (Table 1). For example, the introduction of hnRAC18I of the iodine atom on the benzene ring of Phe8 induces the formation of an intramolecular C–I··· π halogen bonds, thereby locking the peptide chain in a single conformation, and the cross-sectional structure of the assembled fibers is square. The introduction of hnRAC12I of iodine atom on the benzene ring of Phe2 with strong flexibility in the surrounding area, or the introduction of hnRAC12I8I of iodine atom on both the benzene ring of Phe2 and the benzene ring of Phe8, will form multiple different types of intermolecular halogen bonds, inducing the production of a variety of peptide chain conformations. The interface of the fibers formed by the assembly of hnRAC12I and hnRAC12I8I has a petal-shaped structure (Figure 2). Furthermore, based on the understanding of the atomic structure and self-assembly mechanism of hnRAC1 and three different iodide polypeptide fibers, the researchers obtained iodide peptides DIP2I8I amyloid fibers with a completely new structure through rational design (Figure 2).
In summary, this study reveals the key role of halogenation modification in regulating peptide self-assembly and inducing peptide formation of amyloid fiber "kaleidoscope" structure. This study provides important clues and exploration directions for the creation of amyloid fiber nanomaterials with different atomic structure and material properties by accurately designing peptides of different modifications. The research work is supported by the National Natural Science Foundation of China, the Ministry of Science and Technology, and the Shanghai Municipal Science and Technology Commission.
▲Figure 1. Five amyloid fibers with different structures induced by iodination modification
▲Table 1. Intramolecular and intermolecular interactions and thermal stability of hnRAC1 fibers, three iodinated hnRAC1 fibers, and DIP2I8I fibers
▲Figure 2. Schematic diagram of fiber structure assembled from native peptides, modified peptides, and designed peptides. The introduction of iodine atoms at different locations of the peptide produces a variety of different peptide chain structures and is further arranged into different fiber structures.
Source: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences