Methyl transfer by substrate signaling from a knotted protein fold
| Autor: | Takuhiro Ito, Erika A. Taylor, Reiko Sakaguchi, Ya-Ming Hou, Thomas Christian, Agata P. Perlinska, Shigeyuki Yokoyama, Georges Lahoud, Joanna I. Sulkowska |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protein Folding S-Adenosylmethionine Methyltransferase Protein Conformation Biology Molecular Dynamics Simulation Article Catalysis Substrate Specificity Quantitative Biology::Subcellular Processes 03 medical and health sciences Molecular dynamics Protein structure stomatognathic system RNA Transfer Structural Biology Escherichia coli Molecular Biology Quantitative Biology::Biomolecules tRNA Methyltransferases Quantitative Biology::Molecular Networks Escherichia coli Proteins RNA food and beverages Mathematics::Geometric Topology TRNA Methyltransferases 030104 developmental biology surgical procedures operative Structural biology Biophysics Protein folding |
| Zdroj: | Nature structuralmolecular biology. 23(10) |
| ISSN: | 1545-9985 |
| Popis: | Proteins with knotted configurations are restricted in conformational space relative to unknotted proteins. Little is known if knotted proteins have sufficient dynamics to communicate between spatially separated substrate-binding sites. In bacteria, TrmD is a methyl transferase that uses a knotted protein fold to catalyze methyl transfer from S-adenosyl methionine (AdoMet) to G37-tRNA. The product m1G37-tRNA is essential for life as a determinant to maintain protein synthesis reading-frame. Using an integrated approach of structure, kinetic, and computational analysis, we show here that the structurally constrained TrmD knot is required for its catalytic activity. Unexpectedly, the TrmD knot has complex internal movements that respond to AdoMet binding and signaling. Most of the signaling propagates the free energy of AdoMet binding to stabilize tRNA binding and to assemble the active site. This work demonstrates new principles of knots as an organized structure that captures the free energies of substrate binding to facilitate catalysis. |
| Databáze: | OpenAIRE |
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