Evolution of a protein interaction domain family by tuning conformational flexibility
| Autor: | Brian F. Volkman, Kenneth E. Prehoda, Dustin S. Whitney |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Guanylate kinase Protein Conformation Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Biochemistry Catalysis Article 03 medical and health sciences Molecular dynamics Colloid and Surface Chemistry Protein structure Peptide bond Protein Interaction Domains and Motifs Binding site Nuclear Magnetic Resonance Biomolecular Flexibility (engineering) chemistry.chemical_classification Chemistry General Chemistry 0104 chemical sciences 030104 developmental biology Enzyme Biophysics Guanylate Kinases Function (biology) |
| Popis: | Conformational flexibility allows proteins to adopt multiple functionally important conformations, but can also lead to non-functional structures. We analyzed the dynamic behavior of the enzyme Guanylate Kinase as it evolved into the GK protein interaction domain (GKPID) to investigate the role of flexibility in the evolution of new protein functions. We found that the ancestral enzyme is very flexible, allowing it to adopt open conformations that can bind nucleotide and closed ones that enable catalysis of phosphotransfer from ATP to GMP. Historical mutations that converted the GK from an enzyme to a protein interaction domain dramatically reduce flexibility, predominantly by inhibiting rotations of the protein backbone that are coupled to the global closing motion. Removing flexibility prevents adoption of conformations that cannot fit the protein partner in the binding site. Our results highlight the importance of mutations that optimize protein conformational flexibility with function during evolution. |
| Databáze: | OpenAIRE |
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