Role of peptides in prebiotic chemistry


Localizing RNA to membranes


In primitive cells, membranes may have played a catalytic role by co-localizing reactants on their surface. For example, the localization of RNAs to membranes could promote ribozyme assembly and facilitate ribozyme catalysis. Such a scenario relies upon a simple mechanism to anchor the RNA onto the protocell membrane. Our studies showed that short, cationic, amphipathic peptides can drive RNA binding to both zwitterionic phospholipid and anionic fatty acid membranes. The association of these cationic peptides with phospholipid vesicles can enhance the local positive charge on a membrane and attract RNA polynucleotides. This discovery opens the door to studying membrane-localized prebiotic reactions with RNA catalysts or substrates.



Electrostatic localization of RNA to protocell membranes by cationic hydrophobic peptides.

Assisting nonenzymatic RNA replication by slowing stranding annealing

To enable repeated cycles of RNA replication, the two strands of the product must be separated and then copied before they reanneal. In solution, complementary RNA strands anneal orders of magnitude more rapidly than non-enzymatic template copying, rendering multiple rounds of RNA replication a formidable challenge. Our recent studies enabled further rounds of copying by using oligoarginine peptides. These peptides slow the annealing of complementary RNAs by up to several thousand-fold while still allowing short primers and activated monomers to bind to template strands. As a result template-directed primer extension can proceed even in the presence of the complementary strand to the template. Remarkably, the template copying occurs within a phase-separated condensed state, or coacervate. Future work will focus on elucidating the molecular mechanism of this unusual RNA-peptide interaction.



Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication.


Driving vesicle growth


In addition to these structural roles, peptides can also play a catalytic role in driving vesicle growth. We showed that a simple dipeptide catalyst seryl-histidine (Ser-His) can drive vesicle growth through the catalytic synthesis of a hydrophobic dipeptide, N-acetyl-L-phenylalanine leucinamide, which localizes to the membrane of model protocells and drives competitive vesicle growth in a manner similar to that demonstrated previously for phospholipids. We are currently exploring other simple peptide catalysts that could enable the origin of selection and competition between protocells.



Collaboration between primitive cell membranes and soluble catalysts.

Competition between model protocells driven by an encapsulated catalyst.

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