title: Specificity and catalysis hardwired at the RNA-protein interface in a translational proofreading enzyme.
abstract: Proofreading modules of aminoacyl-tRNA synthetases are responsible for enforcing a high fidelity during translation of the genetic code. They use strategically positioned side chains for specifically targeting incorrect aminoacyl-tRNAs. Here, we show that a unique proofreading module possessing a D-aminoacyl-tRNA deacylase fold does not use side chains for imparting specificity or for catalysis, the two hallmark activities of enzymes. We show, using three distinct archaea, that a side-chain-stripped recognition site is fully capable of solving a subtle discrimination problem. While biochemical probing establishes that RNA plays the catalytic role, mechanistic insights from multiple high-resolution snapshots reveal that differential remodelling of the catalytic core at the RNA-peptide interface provides the determinants for correct proofreading activity. The functional crosstalk between RNA and protein elucidated here suggests how primordial enzyme functions could have emerged on RNA-peptide scaffolds before recruitment of specific side chains.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Sadeem
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Sowndarya
authors.initials: S
authors.lastname: Muthukumar
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Kuncha
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Satya Brata
authors.initials: SB
authors.lastname: Routh
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Antony S K
authors.initials: AS
authors.lastname: Yerabham
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Tanweer
authors.initials: T
authors.lastname: Hussain
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Venu
authors.initials: V
authors.lastname: Kamarthapu
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Shobha P
authors.initials: SP
authors.lastname: Kruparani
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Sankaranarayanan
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D008958:Models, Molecular; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000378:metabolism*; D017393:RNA Editing / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D012313:RNA; D000604:Amino Acyl-tRNA Synthetases