Biology subjects

Verner, V.

Publications and source records attributed to Verner, V..

3 recordsLinked to original sources

bioRxiv2026

Protoribosomal condensate formation across cationic chemistries

Early ribonucleoprotein systems likely required mechanisms to concentrate and organize RNA. Modern ribosomes use Mg2+ and evolved Lys/Arg-rich protein extensions to stabilize their RNA backbone. Before templated synthesis, however, peptide formation likely generated heterogeneous sequence populations rather than reproducible ribosomal sequences. Here, we compare Mg2+, ribosomal peptides, and statistical peptide libraries in organizing a 136-nucleotide model of the peptidyl transferase center (sPTC). Mg2+ condenses sPTC only at a large excess of positive charge following thermal annealing, producing largely arrested libraries. Acidic conditions further promote condensation. Ribosomal peptides instead promote coacervation near charge stoichiometry and form droplets that readily fuse. Several statistical peptide libraries also coacervate with sPTC, despite comprising heterogenous mixtures rather than a single defined sequence. Increasing mean positive charge favors condensation, but Lys/Arg-containing libraries undergo liquid-liquid phase separation more readily and across broader conditions than matched libraries containing the prebiotically plausible diaminopropionic acid (Dpr) and diaminobutyric acid (Dab). Atomistic computer simulations implicate Arg as a major source of this difference, as it can form more numerous and longer-lived hydrogen bonds with RNA, while competitive partitioning experiments show preferential condensate recruitment in the order Arg > Lys > Dab > Dpr. Together, our findings show that peptide-RNA coacervation can be triggered collectively by statistical peptide ensembles, providing a plausible route to protoribosomal organization without peptide sequence-specific optimization. Cationic chemistry shapes condensate formation and material properties, suggesting that amino acid alphabet formation could have broadened the conditions supporting liquid-like protoribosomal assemblies.

biochemistry↗

bioRxiv2026

Xeno amino acid alphabets form peptides with familiar secondary structure

Summary paragraphThe central dogma of molecular biology describes how genetic information stored in nucleic acids guides the formation of structured proteins from a single molecular alphabet of twenty amino acids (C20)1,2. The extent to which C20 is uniquely capable of forming structural polymers remains a fundamental open question. Here we demonstrate that peptides built from other, "xeno" amino acid alphabets can adopt protein-like secondary structural motifs. Having designed two different xeno alphabets, with them we constructed both combinatorial random sequence libraries and specific, designed 25-mer sequences. We report sequence-dependent structural motifs that result according to circular dichroism, infrared spectroscopy and nuclear magnetic resonance interpreted by molecular dynamics simulations, supported by extensive quantum mechanical calculations. This evidence, including a solution-phase NMR-resolved helical motif, demonstrates that the potential for amino acids to form structure bearing sequences is not unique to lifes alphabet, and thereby reveals a previously unexplored sequence-structure space. Results inform the search for extraterrestrial life, lay foundations for incorporating novel synthetic functional groups and heteroatoms into structure-bearing alphabets, and provide the first truly independent data with which to test and improve all that has been learned about protein folding from the study of lifes 20 side chains.

biochemistry↗

bioRxiv2025

Prebiotically Plausible Peptides can Self-assemble into β-rich Nanostructures

Peptides can self-assemble into diverse morphologies in a programmable manner and hence are privileged building blocks used widely in nanotechnology. Most reported peptide nanostructures consist of one (or a few) defined sequence(s), as self-similarity is presumed to be essential for promoting assembly. While oligomerisation is seen as an important feature of the earliest functional polymers during the origin of life, prebiotic peptides were likely short, statistical, and non-templated - traits that seem incommensurate with robust self-assembly. Here we show that random 25-mer peptides can efficiently and spontaneously form highly thermostable, soluble assemblies rich with beta-sheets. Notably, these nanostructures only emerge when random peptides are constructed with an early alphabet, consisting of the 10 canonical amino acids that were also prebiotically abundant - but not other alphabets tested. Hence, our findings show that peptide self-assembly does not require purity, and in fact compositional complexity is adaptive for preventing formation of insoluble structures. Altogether, this study showcases that unevolved sequences of prebiotically-abundant amino acids can readily produce foldable self-assembling polymers, thereby providing a potential steppingstone toward the first proteins, prior to the onset of purifying selection.

biochemistry↗