Amyloid and the origin of life: self-replicating catalytic amyloids as prebiotic informational and protometabolic entities

Abstract

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.

Keywords: Amyloid world; Molecular evolution; Origin-of-life theory; Primordial genetics; Prion; RNA world.

Fig. 1

Schematic representation of the β-sheet structure of amyloid. a Section of a β-pleated sheet. The β-strands, which run perpendicular to the long axis of the fibril, are marked in green and interstrand hydrogen bonds in red. b Hydrogen-bonding pattern of two antiparallel β-strands. c Antiparallel bilayered β-sheet. d Parallel bilayered β-sheet. Typically, the repeating unit of the amyloid fibrils consists of two tightly packed layers of β-sheets with side chains within the bilayers forming a dry interdigitating zipper interface. The zippers differ in the organization of the β-strands within and between the β-sheets and in the stacking of the β-sheets enabling the formation of a diversity of structural variants. The cross β-structure gives rise to a characteristic X-ray diffraction pattern with a meridional reflection at 0.48 nm and an equatorial reflection at about 1.0 nm. These reflections correspond to the interstrand and intersheet spacings, respectively. The mature amyloid fibril is a highly ordered linear supramolecular structure forming long unbranched fibrils ranging from 5 to 12 nm in diameter. References are given in the text

Fig. 2

Schematic representation of the amyloid model of the origin of life. The figure outlines the proposed pathway of one type of peptide monomer from a prebiotic mixture of various protopeptides. The nucleation-dependent replication system is in-put sensitive, chiroselective, and error correcting. An initial slow nucleation process is followed by a fast polymerization phase where peptide monomers are added the growing end of the protofilament. Fragmentation generates new seeds that can initiate repeated replication cycles. The same peptide monomer can give rise to different amyloid structures and molecular rearrangements are possible. Specific conformational changes can be replicated in the fibril/protofibril-catalyzed cycle II. Amyloid is also able to direct the synthesis of its own constituent peptides. The β-sheet conformers and ribonucleotides interact dynamically and cooperatively, and the amyloid-based supramolecular fibrillar assemblies can function as a primitive metabolic apparatus catalyzing the formation metabolite precursors. The model does not exclude the possibility an extraterrestrial origin of the primordial amino acids or a contribution of extraterrestrial amino acids to the terrestrial prebiotic amino acid pool. References are given in the text

Fig. 3

Electron micrograph of a polymorphic fibrillar amyloid network self-assembled from a prebiotically relevant 9-mer peptide (EGGSVVAAD) in aqueous environment. Experimental conditions were as described in Ref. [10]