Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS
| Autor: | Xiang-Lei Yang, Litao Sun, Paul Schimmel, David Blocquel, Youngzee Song |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular endocrine system Archaeal Proteins Static Electricity Computational biology Biology 010402 general chemistry Crystallography X-Ray 01 natural sciences Evolution Molecular 03 medical and health sciences chemistry.chemical_compound Protein Domains Animals Humans Amino Acid Sequence Protein Structure Quaternary Conserved Sequence chemistry.chemical_classification Multidisciplinary Binding Sites Sequence Homology Amino Acid Aminoacyl tRNA synthetase Alternative splicing Alanine-tRNA Ligase DNA Biological Sciences 0104 chemical sciences Amino acid Crystallography Alternative Splicing Kinetics 030104 developmental biology chemistry Docking (molecular) Archaeoglobus fulgidus Transfer RNA Protein Multimerization |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 113(50) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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