Amyloid Assemblies: Protein Legos at a Crossroads in Bottom‐Up Synthetic Biology

Abstract

One of the major objectives that bottom-up synthetic biology shares with chemical biology is to engineer extant biological molecules to implement novel functionalities in living systems. Proteins, due to their astonishing structural and functional versatility and to their central roles in the biology of cells, should be cornerstones of synthetic biology. In particular, protein amyloid cross-β assemblies constitute one of the most stable, conceptually simple and universal macromolecular architectures ever found in Nature and thus have enormous potential to be explored. This article focuses on the concepts behind the use of the amyloid cross-β-structural framework as a synthetic biology part, underlining recent basic findings and ideas. The pros and the cons associated with the polymorphism and the cellular toxicity of protein amyloids are also discussed, keeping in mind the possible suitability of these protein assemblies for scaffolding novel orthogonal macromolecular devices in vivo.

PASTA 2.0: an improved server for protein aggregation prediction

“…Finally, it is now possible to calculate the difference in aggregation propensity after point-mutations and between different protein pairs, allowing the analysis of pathogenic mutations and of cross-amyloid interactions between protein heterodimers, as suggested e.g. by (16) and (17), respectively. To assess the effect of point-mutations on the aggregation profile, a free energy profile is now present in output, together with the probability profile already present in the old server.…”

Self-Assembled Amyloid-Like Oligomeric-Cohesin Scaffoldin for Augmented Protein Display on the Saccharomyces cerevisiae Cell Surface

“…It is known that the property of the C-terminal protein appended to the Ure2p fibrillogenic domain can have a considerable effect on fibril formation (1,2,4). It is also important to incorporate an appropriate linker between the fibrillogenic domain and the appended cargo protein to avoid steric hindrance that may hamper proper packaging of the cross-beta sheets to form an ordered fibril structure with a properly oriented C-terminal cargo protein (10). The HD domain (first X2 module) is found directly linked upstream of the first cohesin module in the C. cellulolyticum CipC scaffoldin.…”

Gene Network Construction for Molecular Regulation

“…Szybalski and Skalka described that the work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes but also leads us into the new era of "synthetic biology," in which existing genes are described and analyzed and new gene arrangements can be constructed and evaluated. 51 Synthetic biology aims to design modules and devices, based either on natural or artificially modified macromolecular parts, enabling novel functionalities in reconstructed biological systems, or in those built de novo 52,54 One of the major objectives of bottom-up synthetic biology is to engineer extant biological molecules to implement novel functionalities in living systems. 52,54 Engineering novel reusable gene networks to provide a greater control over cellular processes is one of the goals of the emerging discipline of synthetic biology.…”

“…51 Synthetic biology aims to design modules and devices, based either on natural or artificially modified macromolecular parts, enabling novel functionalities in reconstructed biological systems, or in those built de novo 52,54 One of the major objectives of bottom-up synthetic biology is to engineer extant biological molecules to implement novel functionalities in living systems. 52,54 Engineering novel reusable gene networks to provide a greater control over cellular processes is one of the goals of the emerging discipline of synthetic biology. 55−57 Gene network engineers work with a framework in which a network is designed based on a simplified mathematical model, constructed using tools from molecular biology, deployed within a suitable host, and experimentally validated against the mathematical abstraction.…”