Chiral checkpoints during protein biosynthesis

Abstract

Edited by Karin Musier-Forsyth Protein chains contain only L-amino acids, with the exception of the achiral glycine, making the chains homochiral. This homochirality is a prerequisite for proper protein folding and, hence, normal cellular function. The importance of D-amino acids as a component of the bacterial cell wall and their roles in neurotransmission in higher eukaryotes are well-established. However, the wider presence and the corresponding physiological roles of these specific amino acid stereoisomers have been appreciated only recently. Therefore, it is expected that enantiomeric fidelity has to be a key component of all of the steps in translation. Cells employ various molecular mechanisms for keeping D-amino acids away from the synthesis of nascent polypeptide chains. The major factors involved in this exclusion are aminoacyl-tRNA synthetases (aaRSs), elongation factor thermo-unstable (EF-Tu), the ribosome, and D-aminoacyl-tRNA deacylase (DTD). aaRS, EF-Tu, and the ribosome act as "chiral checkpoints" by preferentially binding to L-amino acids or L-aminoacyl-tRNAs, thereby excluding D-amino acids. Interestingly, DTD, which is conserved across all life forms, performs "chiral proofreading," as it removes D-amino acids erroneously added to tRNA. Here, we comprehensively review D-amino acids with respect to their occurrence and physiological roles, implications for chiral checkpoints required for translation fidelity, and potential use in synthetic biology. The authors declare that they have no conflicts of interest with the contents of this article.

Antibacterial Activity and Mechanism of Linalool against Shewanella putrefaciens

“…The aminoacyl–tRNA biosynthetic pathway is a part of the protein synthesis translation pathway [ 50 ]. Amino acids carried by aminoacyl–tRNA are coupled by peptide bonds in ribosomes in a specific order according to the mRNA sequence, and this step plays a key role in protein biosynthesis [ 51 ]. Interference in the aminoacyl–tRNA synthesis pathway affects the related protein synthesis pathway and consequently the cell proliferation and signal transduction [ 52 ].…”

Recruitment of archaeal DTD is a key event toward the emergence of land plants

“…Elongation factor thermo unstable (EF-Tu) is one of the most abundant proteins of the cell and is known to bind l -aa-tRNAs with higher affinity compared to d -aa-tRNAs ( 35 ). d -aa-tRNAs are discriminated by the EF-Tu and other cellular chiral checkpoints ( 36 ). To test EF-Tu’s ability to protect l -aa-tRNAs from freely diffusing acetaldehyde, we performed modification experiments in the presence of EF-Tu.…”

A consequence of drug targeting of aminoacyl‐tRNA synthetases in Mycobacteriumtuberculosis

“…Aminoacyl‐tRNA synthetases are one of the important ancient ‘house‐hold’ enzymes which appeared during the early evolution of the translational machinery and act as a bridge between the RNA and proteins (Kuncha et al, 2019). They dictate the genetic code by specifically adding amino acids to the tRNAs (Fry, 2016).…”

“…In most systems, there are pools of synthetases most often up to 20 (Fry, 2016), which correspond to 20 amino acids (Guo and Schimmel, 2012; Ibba and Söll, 2000; Ogle and Ramakrishnan, 2005). The precision in translation largely depends on the fidelity of these enzymes (Hayashi et al, 1991; Kuncha et al, 2019). Usually, the anticodon‐binding domain of an aminoacyl‐tRNA synthetase recognizes the cognate tRNA (Kuncha et al, 2019), except for Alanyl‐tRNA synthetase (Ala‐RS) and Seryl‐tRNA synthetase (Ser‐RS) (Kuncha et al, 2019), in this case, the acceptor arm G3•U70 and the variable arm are recognized respectively (Giege et al, 1998; Hou and Schimmel, 1988).…”