RESUMEN
The close synergy between peptides and nucleic acids in current biology is suggestive of a functional co-evolution between the two polymers. Here we show that cationic proto-peptides (depsipeptides and polyesters), either produced as mixtures from plausibly prebiotic dry-down reactions or synthetically prepared in pure form, can engage in direct interactions with RNA resulting in mutual stabilization. Cationic proto-peptides significantly increase the thermal stability of folded RNA structures. In turn, RNA increases the lifetime of a depsipeptide by >30-fold. Proto-peptides containing the proteinaceous amino acids Lys, Arg, or His adjacent to backbone ester bonds generally promote RNA duplex thermal stability to a greater magnitude than do analogous sequences containing non-proteinaceous residues. Our findings support a model in which tightly-intertwined biological dependencies of RNA and protein reflect a long co-evolutionary history that began with rudimentary, mutually-stabilizing interactions at early stages of polypeptide and nucleic acid co-existence.
Asunto(s)
Evolución Molecular , Péptidos/metabolismo , Pliegue de Proteína , Estabilidad del ARN , ARN/metabolismo , Secuencia de Aminoácidos , Aminobutiratos/química , Aminobutiratos/metabolismo , Cationes/química , Cationes/metabolismo , Dicroismo Circular , Hidrólisis , Resonancia Magnética Nuclear Biomolecular , Origen de la Vida , Ornitina/química , Ornitina/metabolismo , Péptidos/química , Estabilidad Proteica , ARN/química , beta-Alanina/análogos & derivados , beta-Alanina/química , beta-Alanina/metabolismoRESUMEN
Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine-linked, analogous to today's proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein-RNA and protein-DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life.
Asunto(s)
Aminoácidos/química , Origen de la Vida , Péptidos/química , Proteínas/química , Aminoácidos/genética , Aminobutiratos/química , Cationes/química , Proteínas de Unión al ADN/química , Depsipéptidos/química , Depsipéptidos/genética , Péptidos/genética , Proteínas/genética , Proteínas de Unión al ARN/química , Electricidad Estática , beta-Alanina/análogos & derivados , beta-Alanina/químicaRESUMEN
Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2, high Fe2+, and high Mn2+) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+, Fe2+, and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ and Mn2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; and (iii) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe2+ and Mn2+ were abundant, these findings suggest that Fe2+ and Mn2+ played a role in early ribosomal evolution.
RESUMEN
BACKGROUND: Managing "spaghetti syndrome," the tangle of therapeutic cables, tubes, and cords at patients' bedsides, can be challenging. OBJECTIVES: To assess nurses' perceptions of the effectiveness of a novel banding device in management of spaghetti syndrome. METHODS: A simple color-coded elastomeric banding strap with ribbed flaps was attached to bed rails of adult critical care patients to help organize therapeutic cables, tubes, wires, and cords. Nurses were surveyed before and after use of the bands and after the nursing shift to assess the burden of spaghetti syndrome and the effectiveness of using the bands. RESULTS: Use of the bands decreased the time spent untangling cords, reduced the frequency of contact of tubing with the floor, and diminished disruptions in care. CONCLUSIONS: Use of a simple flexible latex-free elastomeric band may help organize therapeutic tubing at patients' bedsides and may promote improvements in nursing care.