Abstract:Most self-replicating peptide systems are made of α-helix forming sequences. However, it has been postulated that shorter and simpler peptides may also serve as templates for replication when arranged into well-defined structures. We describe here the design and characterization of new peptides that form soluble β-sheet aggregates that serve to significantly accelerate their ligation and self-replication. We then discuss the relevance of these phenomena to early molecular evolution, in light of additional func… Show more
“…There are additional features that make amyloid interesting in the origin-of-life-context: (i) it is polymorphic in nature and environmentally sensitive (Greenwald and Riek 2010, Eichner and Radford 2011, Toyama and Weissman 2011, (ii) it provides a means for short peptides to become functional under harsh conditions (Maury 2008, Bourbo et al 2011, Rufo et al 2014, and (iii) experimental evidence shows that a peptide with a prebiotically plausible amino acid composition spontaneously forms amyloid structures (Maury et al 2012).…”
The question of the origin of life on Earth can largely be reduced to the question of what was the first molecular replicator system that was able to replicate and evolve under the presumably very harsh conditions on the early Earth. It is unlikely that a functional RNA could have existed under such conditions and it is generally assumed that some other kind of information system preceded the RNA world. Here, I present an informational molecular system that is stable, self-replicative, environmentally responsive, and evolvable under conditions characterized by high temperatures, ultraviolet and cosmic radiation. This postulated pregenetic system is based on the amyloid fold, a functionally unique polypeptide fold characterized by a cross beta-sheet structure in which the beta strands are arranged perpendicular to the fiber axis. Beside an extraordinary structural robustness, the amyloid fold possesses a unique ability to transmit information by a three-dimensional templating mechanism. In amyloidogenesis short peptide monomers are added one by one to the growing end of the fiber. From the same monomeric subunits several structural variants of amyloid may be formed. Then, in a self-replicative mode, a specific amyloid conformer can act as a template and confer its spatially encoded information to daughter molecular entities in a repetitive way. In this process, the specific conformational information, the spatially changed organization, is transmitted; the coding element is the steric zipper structure, and recognition occurs by amino acid side chain complementarity. The amyloid information system fulfills several basic requirements of a primordial evolvable replicator system: (i) it is stable under the presumed primitive Earth conditions, (ii) the monomeric building blocks of the informational polymer can be formed from available prebiotic compounds, (iii) the system is self-assembling and self-replicative and (iv) it is adaptive to changes in the environment and evolvable.
“…There are additional features that make amyloid interesting in the origin-of-life-context: (i) it is polymorphic in nature and environmentally sensitive (Greenwald and Riek 2010, Eichner and Radford 2011, Toyama and Weissman 2011, (ii) it provides a means for short peptides to become functional under harsh conditions (Maury 2008, Bourbo et al 2011, Rufo et al 2014, and (iii) experimental evidence shows that a peptide with a prebiotically plausible amino acid composition spontaneously forms amyloid structures (Maury et al 2012).…”
The question of the origin of life on Earth can largely be reduced to the question of what was the first molecular replicator system that was able to replicate and evolve under the presumably very harsh conditions on the early Earth. It is unlikely that a functional RNA could have existed under such conditions and it is generally assumed that some other kind of information system preceded the RNA world. Here, I present an informational molecular system that is stable, self-replicative, environmentally responsive, and evolvable under conditions characterized by high temperatures, ultraviolet and cosmic radiation. This postulated pregenetic system is based on the amyloid fold, a functionally unique polypeptide fold characterized by a cross beta-sheet structure in which the beta strands are arranged perpendicular to the fiber axis. Beside an extraordinary structural robustness, the amyloid fold possesses a unique ability to transmit information by a three-dimensional templating mechanism. In amyloidogenesis short peptide monomers are added one by one to the growing end of the fiber. From the same monomeric subunits several structural variants of amyloid may be formed. Then, in a self-replicative mode, a specific amyloid conformer can act as a template and confer its spatially encoded information to daughter molecular entities in a repetitive way. In this process, the specific conformational information, the spatially changed organization, is transmitted; the coding element is the steric zipper structure, and recognition occurs by amino acid side chain complementarity. The amyloid information system fulfills several basic requirements of a primordial evolvable replicator system: (i) it is stable under the presumed primitive Earth conditions, (ii) the monomeric building blocks of the informational polymer can be formed from available prebiotic compounds, (iii) the system is self-assembling and self-replicative and (iv) it is adaptive to changes in the environment and evolvable.
“…Interestingly however, there is still little known about the ability of amyloids to perform the functions of enzymes. Macromolecular β-sheet-rich structures formed from basic peptides with simple repetitive sequences have been shown to have phosphodiesterase activity [ 19 , 20 ] and amyloids have been shown to template their own synthesis from two activated peptide precursors [ 21 , 22 ]. With these promising indications, we set out to address the question whether one can systematically explore the catalytic potential of amyloids?…”
Enzymes are capable of directing complex stereospecific transformations and of accelerating reaction rates many orders of magnitude. As even the simplest known enzymes comprise thousands of atoms, the question arises as to how such exquisite catalysts evolved. A logical predecessor would be shorter peptides, but they lack the defined structure and size that are apparently necessary for enzyme functions. However, some very short peptides are able to assemble into amyloids, thereby forming a well-defined tertiary structure called the cross-β-sheet, which bestows unique properties upon the peptides. We have hypothesized that amyloids could have been the catalytically active precursor to modern enzymes. To test this hypothesis, we designed an amyloid peptide library that could be screened for catalytic activity. Our approach, amenable to high-throughput methodologies, allowed us to find several peptides and peptide mixtures that form amyloids with esterase activity. These results indicate that amyloids, with their stability in a wide range of conditions and their potential as catalysts with low sequence specificity, would indeed be fitting precursors to modern enzymes. Furthermore, our approach can be efficiently expanded upon in library size, screening conditions, and target activity to yield novel amyloid catalysts with potential applications in aqueous-organic mixtures, at high temperature and in other extreme conditions that could be advantageous for industrial applications.
“…The fibril-catalyzed step is characterized by an initial fast docking phase followed by a slow structural rearrangement locking phase [ 34 ]. From a prebiotic perspective, the demonstrations of template-assisted ligation of fibrillogenic peptides from two shorter building blocks [ 23 – 25 ] and of amyloid-directed synthesis of its constituent peptides from amino acids [ 26 ] are important. Fig.…”
A crucial stage in the origin of life was the emergence of the first molecular entity that was able to replicate, transmit information, and evolve on the early Earth. The amyloid world hypothesis posits that in the pre-RNA era, information processing was based on catalytic amyloids. The self-assembly of short peptides into β-sheet amyloid conformers leads to extraordinary structural stability and novel multifunctionality that cannot be achieved by the corresponding nonaggregated peptides. The new functions include self-replication, catalytic activities, and information transfer. The environmentally sensitive template-assisted replication cycles generate a variety of amyloid polymorphs on which evolutive forces can act, and the fibrillar assemblies can serve as scaffolds for the amyloids themselves and for ribonucleotides proteins and lipids. The role of amyloid in the putative transition process from an amyloid world to an amyloid–RNA–protein world is not limited to scaffolding and protection: the interactions between amyloid, RNA, and protein are both complex and cooperative, and the amyloid assemblages can function as protometabolic entities catalyzing the formation of simple metabolite precursors. The emergence of a pristine amyloid-based in-put sensitive, chiroselective, and error correcting information-processing system, and the evolvement of mutualistic networks were, arguably, of essential importance in the dynamic processes that led to increased complexity, organization, compartmentalization, and, eventually, the origin of life.
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