Chirality based proofreading systems and their evolutionary implications
APA
(2025). Chirality based proofreading systems and their evolutionary implications. SciVideos. https://scivideos.org/icts-tifr/32817
MLA
Chirality based proofreading systems and their evolutionary implications. SciVideos, Sep. 22, 2025, https://scivideos.org/icts-tifr/32817
BibTex
@misc{ scivideos_ICTS:32817, doi = {}, url = {https://scivideos.org/icts-tifr/32817}, author = {}, keywords = {}, language = {en}, title = {Chirality based proofreading systems and their evolutionary implications}, publisher = {}, year = {2025}, month = {sep}, note = {ICTS:32817 see, \url{https://scivideos.org/icts-tifr/32817}} }
Abstract
Despite the presence and biological role of D-amino acids, the fundamental issue of how proteins are made only with the L-chiral entities was largely ignored. Over the last two decades, it has become clearer as to how multiple ‘Chiral Checkpoints’ work in concert to avoid D-amino acids from getting incorporated into proteins (1, 2). Our recent work has shed light on how chiral proofreading systems have played critical roles in important evolutionary transitions (3, 4). In the first part of my talk, I will introduce the work that came out of the laboratories of two of the pioneers of nucleic acid research in the area of protein biosynthesis, Paul Berg and Donald Crothers, more than half a century back. Their work on the identification of D-aminoacyl-tRNA deacylase (DTD) and ‘Discriminator hypothesis’, respectively, were hugely ahead of their time and were partly against the general paradigm at that time. In both of the above works, the smallest and the only achiral amino acid turned out to be an outlier as DTD can act weakly on glycine charged tRNAs with a unique discriminator base of ‘Uracil’. This peculiar nature of glycine remained an enigma for nearly half a century. With a load of available information on the subject by the turn of the century, our work on ‘chiral proofreading’ mechanisms during protein biosynthesis serendipitously led us to revisit these findings. Our analysis has uncovered an unexpected connection between them that has implications for evolution of different eukaryotic life forms (5) and will be the focus of the second part of my talk.
Selected references:
1. Kuncha, S. K. et al., J. Biol. Chem. 2019 (Review article).
2. Kumar, P. et al. FEBS Letters 2022 (Review article).
3. Gogoi, J. et al. Sci. Adv. 2022.
4. Kumar, P. et al. Proc. Natl. Acad. Sci. (USA) 2023.
5. Kumar, P. and Sankaranarayanan, R. NAR 2024 (Critical Reviews and Perspective article).