Abstract
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.
Highlights
Protein chains contain only L-amino acids, with the exception of the achiral glycine, making the chains homochiral
The major factors involved in this exclusion are aminoacyl-tRNA synthetases, 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
What favored the selection of L-amino acids over D-amino acids and led to biological systems fine-tuning the protein synthesis machinery to use only L-amino acids is still debated
Summary
X Santosh Kumar Kuncha‡§1, X Shobha P. Even though the (R)-form of thalidomide was administered, due to spontaneous racemization, it led to about ϳ10,000 cases of children being born with abnormal limbs [3, 4] Macromolecules such as nucleic acids contain only D-ribose, and proteins are made of only L-amino acids with the exception of achiral glycine. The focus of this review will be on the occurrence of D-amino acids, their importance in different biological processes, and how various components of the translational machinery, such.
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