Role of Aminoacyl-tRNA Synthetases in Infectious Diseases and Targets for Therapeutic Development

2013 ◽  
pp. 293-329 ◽  
Author(s):  
Varun Dewan ◽  
John Reader ◽  
Karin-Musier Forsyth
Keyword(s):  
Infectious Diseases ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Therapeutic Development

scholarly journals The Role of Orthogonality in Genetic Code Expansion

Life ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 58 ◽  
Author(s):  
Pol Arranz-Gibert ◽  
Jaymin R. Patel ◽  
Farren J. Isaacs
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Genetic Code ◽  
Cross Reactivity ◽  
Elongation Factors ◽  
Translational Machinery ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Genetic Code Expansion

The genetic code defines how information in the genome is translated into protein. Aside from a handful of isolated exceptions, this code is universal. Researchers have developed techniques to artificially expand the genetic code, repurposing codons and translational machinery to incorporate nonstandard amino acids (nsAAs) into proteins. A key challenge for robust genetic code expansion is orthogonality; the engineered machinery used to introduce nsAAs into proteins must co-exist with native translation and gene expression without cross-reactivity or pleiotropy. The issue of orthogonality manifests at several levels, including those of codons, ribosomes, aminoacyl-tRNA synthetases, tRNAs, and elongation factors. In this concept paper, we describe advances in genome recoding, translational engineering and associated challenges rooted in establishing orthogonality needed to expand the genetic code.

scholarly journals Study of the role of the acceptor stem in the interactions between tRNAs and aminoacyl-tRNA synthetases

1975 ◽  
Vol 2 (2) ◽  
pp. 211-222 ◽  
Author(s):  
Jacques Bonnet ◽  
Nicole Befort ◽  
Claudine Bollack ◽  
Franco Fasiolo ◽  
Jean-Pierre Ebel
Keyword(s):  
Trna Synthetases ◽  
Acceptor Stem ◽  
Aminoacyl Trna Synthetases

scholarly journals Aminoacyl-tRNA synthetases and aminoacylation of tRNA in the nucleus.

2002 ◽  
Vol 49 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Piotr Mucha
Keyword(s):  
Living Cell ◽  
Eukaryotic Cell ◽  
Spatial Segregation ◽  
Elongation Factors ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
New Findings ◽  
Translation Apparatus ◽  
The World

This review is focused on findings concerning the presence of translation apparatus components (aminoacyl-tRNA synthetases, aminoacyl-tRNA, elongation factors) as well as translation itself in the nucleus. A nuclear role of these molecules is unknown. New findings suggest that well-accepted model of spatial segregation of transcription and translation in eukaryotic cell may be oversimplifcation. Nuclear coupling of both these processes show us how exciting and surprising may be the world of the living cell.

The use of neutrons to study protein-RNA interactions

1980 ◽  
Vol 290 (1043) ◽  
pp. 627-633 ◽  
Keyword(s):  
Structural Information ◽  
Viral Proteins ◽  
Globular Proteins ◽  
Specific Interactions ◽  
Trna Synthetases ◽  
Structural Modifications ◽  
Aminoacyl Trna Synthetases ◽  
Simultaneous Study ◽  
And Function

Protein-RNA interactions play a key role in the structure, morphogenesis and function of various systems (viruses, ribosomes and, more generally, protein synthesis). The neutron is a powerful tool to study those interactions. Some examples, are given. For viruses, neutrons provide structural information on the two molecules where they interact. Viral proteins do not appear to be simple globular proteins. In the interactions between tRNA and aminoacyl tRNA synthetases, neutrons allow a simultaneous study of the reaction and of the structural modifications associated with that reaction, giving a hint on the role of both electrostatic and specific interactions.

scholarly journals Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS

2016 ◽  
Vol 113 (50) ◽  
pp. 14300-14305 ◽  
Author(s):  
Litao Sun ◽  
Youngzee Song ◽  
David Blocquel ◽  
Xiang-Lei Yang ◽  
Paul Schimmel
Keyword(s):  
Dna Binding ◽  
Crystal Structures ◽  
Sequence Divergence ◽  
Dimer Interface ◽  
Trna Synthetases ◽  
X Ray Scattering ◽  
Aminoacyl Trna Synthetases ◽  
Single Exception ◽  
Binding Groove

The 20 aminoacyl tRNA synthetases (aaRSs) couple each amino acid to their cognate tRNAs. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence. In human cells, C-Ala is also a splice variant of AlaRS. Crystal structures of two forms of human C-Ala, and small-angle X-ray scattering of AlaRS, showed that the large sequence divergence of human C-Ala reshaped C-Ala in a way that changed the global architecture of AlaRS. This reshaping removes the role of C-Ala in prokaryotes for docking tRNA and instead repurposes it to form a dimer interface presenting a DNA-binding groove. This groove cannot form with the bacterial ortholog. Direct DNA binding by human C-Ala, but not by bacterial C-Ala, was demonstrated. Thus, instead of acquiring a novel appended domain like other human aaRSs, which engendered novel functions, a new AlaRS architecture was created by diversifying a preexisting appended domain.

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