Untying a Protein Knot by Circular Permutation
Autor: | Ping-Chiang Lyu, Shang-Te Danny Hsu, I-Chen Hu, Ya-Chu Chuang |
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Rok vydání: | 2018 |
Předmět: |
Protein Folding
Protein Conformation Ligands Quantitative Biology::Subcellular Processes Combinatorics Knot (unit) stomatognathic system Structural Biology Molecular Biology Topology (chemistry) Physics Quantitative Biology::Biomolecules food and beverages A protein Robustness (evolution) RNA Proteins Methyltransferases Circular permutation in proteins Mathematics::Geometric Topology Folding (chemistry) Kinetics surgical procedures operative Protein folding Peptides Protein Binding |
Zdroj: | Journal of molecular biology. 431(4) |
ISSN: | 1089-8638 |
Popis: | Topologically knotted proteins are tantalizing examples of how polypeptide chains can explore complex free energy landscapes to efficiently attain defined knotted conformations. The evolution trails of protein knots, however, remain elusive. We used circular permutation to change an evolutionally conserved topologically knotted SPOUT RNA methyltransferase into an unknotted form. The unknotted variant adopted the same three-dimensional structure and oligomeric state as its knotted parent, but its folding stability was markedly reduced with accelerated folding kinetics and its ligand binding was abrogated. Our findings support the hypothesis that the universally conserved knotted topology of the SPOUT superfamily evolved from unknotted forms through circular permutation under selection pressure for folding robustness and, more importantly, for functional requirements associated with the knotted structural element. |
Databáze: | OpenAIRE |
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