Biology subjects

Kaur, S.

Publications and source records attributed to Kaur, S..

3 recordsLinked to original sources

bioRxiv2018

Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition

In eukaryotic translation initiation AUG recognition of the mRNA requires accommodation of Met-tRNAi in a \"PIN\" state, which is antagonized by the factor eIF1. eIF5 is a GTPase activating protein (GAP) of eIF2 that additionally promotes stringent AUG selection, but the molecular basis of its dual function was unknown. We present a cryo-electron microscopy (cryo-EM) reconstruction of a 48S pre-initiation complex (PIC), at an overall resolution of 3.0 [A], featuring the N-terminal domain (NTD) of eIF5 bound to the 40S subunit at the location vacated by eIF1. eIF5 interacts with and allows a more accommodated orientation of Met-tRNAi. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNAi interaction influenced initiation at near-cognate UUG codons in vivo, and the closed/open PIC conformation in vitro, consistent with direct stabilization of the codon:anticodon duplex by the wild-type eIF5-NTD. The present structure reveals the basis for a key role of eIF5 in start-codon selection.

biophysics↗

bioRxiv2017

Development and molecular characterization of wheat-Aegilops peregrina Introgression Lines with resistance to leaf rust and stripe rust

A wild non-progenitor species from wheat tertiary gene pool Aegilops peregrina accession pau3519 (UUSS) was used for introgression of leaf rust and stripe rust resistance in bread wheat. It was crossed and backcrossed with hexaploid wheat line Chinese Spring PhI to develop two homozygous BC2F6 wheat-Ae. peregrina introgression lines (ILs) viz. IL pau16058 and IL pau16061 through induced homoeologous recombination. Homozygous lines were screened against six Puccinia triticina and two Puccinia striiformis f. sp. tritici pathotypes at the seedling stage and a mixture of prevalent pathotypes of both rust pathogens at the adult plant stage. IL pau16061 showed resistance to leaf rust only while IL pau16058 was resistant to both leaf and stripe rust pathotypes throughout plant life. Molecular characterization of these ILs aided in defining the introgressed regions. Identification of linked markers with advance genomic technologies will aid in marker assisted pyramiding of alien genes in cultivated wheat background.

genetics↗

bioRxiv2016

Drug repurposing for ageing research using model organisms

Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against ageing, despite many genes and pathways shown to be important in the ageing process and numerous studies demonstrating that genetic interventions can lead to a healthier ageing phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate ageing in the invertebrates C. elegans and Drosophila. Our approach combines information on genetic effects on ageing, orthology relationships and sequence conservation, 3D protein structures, drug binding and bioavailability. Overall, we rank 743 different drug-like compounds for their likelihood to modulate ageing. We provide various lines of evidence for the successful enrichment of our ranking for compounds modulating ageing, despite sparse public data suitable for validation. The top ranked compounds are thus prime candidates for in vivo testing of their effects on lifespan in C. elegans or Drosophila. As such, these compounds are promising as research tools and ultimately a step towards identifying drugs for a healthier human ageing.

pharmacology and toxicology↗