Abstract:Ribosome-catalyzed peptide bond formation is a crucial function of all organisms. The ribosome is a ribonucleoprotein particle, with both RNA and protein components necessary for the various steps leading to protein biosynthesis. Evolutionary theory predicts an early environment devoid of complex biomolecules, and prebiotic peptide synthesis would have started in a simple way. A fundamental question regarding peptide synthesis is how the current ribosome-catalyzed reaction evolved from a primitive system. Here… Show more
“…L-amino acid specific tRNA aminoacylation by aaRSs is a crucial step in modern translation. Once L-amino acid charged tRNAs are formed, they are used to synthesize proteins composed of L-amino acids ( 8 ). Modern aaRSs are highly specific in the incorporation of cognate (L-)amino acid because they have specific active sites for substrates, i.e.…”
The origin of homochirality in L-amino acid in proteins is one of the mysteries of the evolution of life. Experimental studies show that a non-enzymatic aminoacylation reaction of an RNA minihelix has a preference for L-amino acid over D-amino acid. The reaction initiates by approaching of a 3′-oxygen of the RNA minihelix to the carbonyl carbon of an aminoacyl phosphate oligonucleotide. Here, employing molecular dynamics simulations, we examined the possible mechanisms that determine this chiral selectivity. The simulation system adopted a geometry required for the chemical reaction to occur more frequently with L-alanine than that with D-alanine. For L-alanine, the structure with this geometry was formed by a combination of stable dihedral angles along alanyl phosphate backbone with a canonical RNA structure, where the methyl group of alanine was placed on the opposite side of the approaching 3′-hydroxyl group with respect to the carbonyl plane. For D-alanine, the methyl group and the 3′-hydroxyl group were placed on the same side with respect to the carbonyl plane, which significantly decreased its ability to approach 3′-oxygen close to the carbonyl carbon compared to L-alanine. The mechanism suggested herein can explain experimentally observed chiral preferences.
“…L-amino acid specific tRNA aminoacylation by aaRSs is a crucial step in modern translation. Once L-amino acid charged tRNAs are formed, they are used to synthesize proteins composed of L-amino acids ( 8 ). Modern aaRSs are highly specific in the incorporation of cognate (L-)amino acid because they have specific active sites for substrates, i.e.…”
The origin of homochirality in L-amino acid in proteins is one of the mysteries of the evolution of life. Experimental studies show that a non-enzymatic aminoacylation reaction of an RNA minihelix has a preference for L-amino acid over D-amino acid. The reaction initiates by approaching of a 3′-oxygen of the RNA minihelix to the carbonyl carbon of an aminoacyl phosphate oligonucleotide. Here, employing molecular dynamics simulations, we examined the possible mechanisms that determine this chiral selectivity. The simulation system adopted a geometry required for the chemical reaction to occur more frequently with L-alanine than that with D-alanine. For L-alanine, the structure with this geometry was formed by a combination of stable dihedral angles along alanyl phosphate backbone with a canonical RNA structure, where the methyl group of alanine was placed on the opposite side of the approaching 3′-hydroxyl group with respect to the carbonyl plane. For D-alanine, the methyl group and the 3′-hydroxyl group were placed on the same side with respect to the carbonyl plane, which significantly decreased its ability to approach 3′-oxygen close to the carbonyl carbon compared to L-alanine. The mechanism suggested herein can explain experimentally observed chiral preferences.
“…This rate increase has probably a similar origin [203] as the entropy trap role proposed for the ribosome [204]. We can then conceive systems based on RNA oligomers and capable of the properties mentioned in Scheme 39 with an increased efficiency compared to mononucleotides.…”
“…improve peptide polymerization possibilities. The handles (Szathmary 1995), somewhat like the stems of tRNA (Tamura & Alexander 2004, p. 1325), bind to a RNA substrate. Aided by a primitive catalyst (Tamura & Schimmel 2001) the amino acids react to form short defined but uncoded peptides (Schimmel & Henderson 1994).…”
Homochirality is an essential feature of biology, but how it developed in early life remains unclear. Our aim in this paper is to add to the discussion by taking a somewhat arbitrary but definite sequence of events and examining carefully the chirality at each stage. Our scenario for the development of life starts with the prebiotic, continues through a pre-RNA stage to the RNA world. This leads to the development of proteins and then to the incorporation of DNA in RNA–DNA–protein biochemistry.We argue that homochirality probably did not develop prebiotically. We see the likely chiral bifurcation point to be during the development of RNA from an achiral pre-RNA. Surprisingly, we find the driving force for this to be enantiomeric cross-inhibition in which the addition of a ‘wrong-handed’ enantiomer to a growing polymer brings the polymerization to a halt. This, it is often argued, is a serious impediment to the development of chiral purity. We suggest that the sign of handedness at this stage was probably determined by chance. We then point out that homochiral RNA was unlikely by itself to lead to homochiral proteins. We identify the additional nonlinear feature required for bifurcation to be the rapid increase in enzymic power available when the amino acids in proteins approach single handedness and structural features such as α-helices and β-sheets become viable. If this is correct, then the handedness of the protein sector is indeed linked to that of RNA. However, the relative sign of the two handednesses will have depended on the precise stereo-sensitive interaction between the RNA and protein systems. We suggest that the most plausible scenario is via the recently discovered RNA binding sites for amino acids, which are both stereo-selective and have contact with the developing genetic code. The detailed steps that determine the handedness are not yet clear and may be specific to the precise development path.It follows that if biochemistry similar to that on Earth developed extraterrestrially, we would surely have homochirality but at this stage we cannot be sure about the handedness of either the nucleic acid or the protein components.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.