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1.
Theory Biosci ; 143(2): 153-160, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38722466

RESUMO

This study proposes a landscape-based scenario for the origin of viruses and cells, focusing on the adaptability of preexisting replicons from the RNP (ribonucleoprotein) world. The scenario postulates that life emerged in a subterranean "warm little pond" where organic matter accumulated, resulting in a prebiotic soup rich in nucleotides, amino acids, and lipids, which served as nutrients for the first self-replicating entities. Over time, the RNA world, followed by the RNP world, came into existence. Replicators/replicons, along with the nutritious soup from the pond, were washed out into the river and diluted. Lipid bubbles, enclosing organic matter, provided the last suitable environment for replicons to replicate. Two survival strategies emerged under these conditions: cell-like structures that obtained nutrients by merging with new bubbles, and virus-like entities that developed various techniques to transmit themselves to fresh bubbles. The presented hypothesis provides the possibility for the common origin of cells and viruses on rocky worlds hosting liquid water, like Earth.


Assuntos
Origem da Vida , Vírus , Aminoácidos/química , Lipídeos/química , Nucleotídeos , RNA , Evolução Biológica
2.
Molecules ; 26(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34641321

RESUMO

Chondrocalcinosis is a metabolic disease caused by the presence of calcium pyrophosphate dihydrate crystals in the synovial fluid. The goal of our endeavor was to find out whether short peptides could be used as a dissolving factor for such crystals. In order to identify peptides able to dissolve crystals of calcium pyrophosphate, we screened through a random library of peptides using a phage display. The first screening was designed to select phages able to bind the acidic part of alendronic acid (pyrophosphate analog). The second was a catalytic assay in the presence of crystals. The best-performing peptides were subsequently chemically synthesized and rechecked for catalytic properties. One peptide, named R25, turned out to possess some hydrolytic activity toward crystals. Its catalysis is Mg2+-dependent and also works against soluble species of pyrophosphate.


Assuntos
Pirofosfato de Cálcio/química , Peptídeos/farmacologia , Alendronato , Hidrólise , Modelos Moleculares , Simulação de Dinâmica Molecular , Biblioteca de Peptídeos , Peptídeos/análise , Peptídeos/química
3.
Mol Biol Evol ; 38(5): 2088-2103, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33480998

RESUMO

Prions, proteins that can convert between structurally and functionally distinct states and serve as non-Mendelian mechanisms of inheritance, were initially discovered and only known in eukaryotes, and consequently considered to likely be a relatively late evolutionary acquisition. However, the recent discovery of prions in bacteria and viruses has intimated a potentially more ancient evolutionary origin. Here, we provide evidence that prion-forming domains exist in the domain archaea, the last domain of life left unexplored with regard to prions. We searched for archaeal candidate prion-forming protein sequences computationally, described their taxonomic distribution and phylogeny, and analyzed their associated functional annotations. Using biophysical in vitro assays, cell-based and microscopic approaches, and dye-binding analyses, we tested select candidate prion-forming domains for prionogenic characteristics. Out of the 16 tested, eight formed amyloids, and six acted as protein-based elements of information transfer driving non-Mendelian patterns of inheritance. We also identified short peptides from our archaeal prion candidates that can form amyloid fibrils independently. Lastly, candidates that tested positively in our assays had significantly higher tyrosine and phenylalanine content than candidates that tested negatively, an observation that may help future archaeal prion predictions. Taken together, our discovery of functional prion-forming domains in archaea provides evidence that multiple archaeal proteins are capable of acting as prions-thus expanding our knowledge of this epigenetic phenomenon to the third and final domain of life and bolstering the possibility that they were present at the time of the last universal common ancestor.


Assuntos
Amiloide/metabolismo , Archaea/genética , Proteínas Arqueais/metabolismo , Epigênese Genética , Príons , Proteínas Arqueais/genética , Domínios Proteicos , Proteoma
4.
Life (Basel) ; 10(7)2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32630714

RESUMO

All life on Earth uses one universal biochemistry stemming from one universal common ancestor of all known living organisms. One of the most striking features of this universal biochemistry is its utter dependence on phosphate group transfer between biochemical molecules. Both nucleic acid and peptide biological synthesis relies heavily on phosphate group transfer. Such dependents strongly indicate very early incorporation of phosphate chemistry in the origin of life. Perhaps as early as prebiotic soup stage. We report here on a short cyclic peptide, c(RPDDHR), designed rationally for pyrophosphate interaction, which is able to create a new amide bond dependent on the presence of pyrophosphate. We believe this result to be a first step in the exploration of Phosphate Transfer Catalysts that must have been present and active in prebiotic soup and must have laid down foundations for the universal bioenergetics.

5.
J Theor Biol ; 470: 101-107, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-30876803

RESUMO

The quest for defining life has lasted since the beginning of modern science. During the last century, we have reached a lot of milestones toward the understanding of life and its molecular basis. Also, as living creatures, we have imprinted awareness about what is life and what is not. It seems like we have everything we need to formulate the definition of life. If so, why has one, that would satisfy everybody, not yet been announced? What is holding us back? Although we seem to know what life is, our understanding of its edges is still blurry. Therefore, author analyses Bernal's stages of biopoiesis and proposes features with Bernoulli distribution so the classification can be as clear-cut as it is possible. Subsequently, the definition of the phenomenon of life based on Shannon's Information Theory is being proposed as a Continuum of the Self-Maintainable Information; and the definition of the living entity as a Distinct Element of that Continuum.


Assuntos
Modelos Biológicos , Origem da Vida , Distribuição Binomial
6.
Astrobiology ; 17(3): 277-285, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28277783

RESUMO

In this paper, we revisit several issues relevant to origin-of-life research and propose a Phosphate Transfer Catalyst hypothesis that furthers our understanding of some of the key events in prebiotic chemical evolution. In the Phosphate Transfer Catalyst hypothesis, we assume the existence of hypothetical metallopeptides with phosphate transfer activity that use abundant polyphosphates as both substrates and energy sources. Nonspecific catalysis by this phosphate transfer catalyst would provide a variety of different products such as phosphoryl amino acids, nucleosides, polyphosphate nucleotides, nucleic acids, and aminoacylated nucleic acids. Moreover, being an autocatalytic set and metabolic driver at the same time, it could possibly replicate itself and produce a collective system of two polymerases; a nucleic acid able to catalyze peptide bond formation and a peptide able to polymerize nucleic acids. The genetic code starts at first as a system that reduces the energy barrier by bringing substrates (2'/3' aminoacyl-nucleotides) together, an ancestral form of the catalysis performed by modern ribosomes. Key Words: Origin of life-Prebiotic chemistry-Catalysis-Nucleic acids. Astrobiology 17, 277-285.


Assuntos
Origem da Vida , Fosfatos/química , Catálise , Modelos Teóricos , Ácidos Nucleicos/química , Peptídeos/química
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