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A Functional Loop Spanning Distant Domains of Glutaminyl-tRNA Synthetase Also Stabilizes a Molten Globule State
- Source :
- Biochemistry. 51:4429-4437
- Publication Year :
- 2012
- Publisher :
- American Chemical Society (ACS), 2012.
-
Abstract
- Molten globule and other disordered states of proteins are now known to play important roles in many cellular processes. From equilibrium unfolding studies of two paralogous proteins and their variants, glutaminyl-tRNA synthetase (GlnRS) and two of its variants [glutamyl-tRNA synthetase (GluRS) and its isolated domains, and a GluRS-GlnRS chimera], we demonstrate that only GlnRS forms a molten globule-like intermediate at low urea concentrations. We demonstrated that a loop in the GlnRS C-terminal anticodon binding domain that promotes communication with the N-terminal domain and indirectly modulates amino acid binding is also responsible for stabilization of the molten globule state. This loop was inserted into GluRS in the eukaryotic branch after the archaea-eukarya split, right around the time when GlnRS evolved. Because of the structural and functional importance of the loop, it is proposed that the insertion of the loop into a putative ancestral GluRS in eukaryotes produced a catalytically active molten globule state. Because of their enhanced dynamic nature, catalytically active molten globules are likely to possess broad substrate specificity. It is further proposed that the putative broader substrate specificity allowed the catalytically active molten globule to accept glutamine in addition to glutamic acid, leading to the evolution of GlnRS.
- Subjects :
- Models, Molecular
Protein Conformation
Protein Stability
Chemistry
Molecular Sequence Data
Equilibrium unfolding
Glutamic acid
Biochemistry
Molten globule
Protein Structure, Tertiary
Amino Acyl-tRNA Synthetases
Glutamate-tRNA Ligase
Crystallography
Protein structure
Transfer RNA
Escherichia coli
Biophysics
Urea
Amino Acid Sequence
Amino acid binding
Peptide sequence
Protein Unfolding
Sequence Deletion
Binding domain
Subjects
Details
- ISSN :
- 15204995 and 00062960
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- Biochemistry
- Accession number :
- edsair.doi.dedup.....b331712bc8b0cc49df53a766a783bccd