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Untying a Protein Knot by Circular Permutation

Author:
Chuang, Ya-Chu, Hu, I-Chen, Lyu, Ping-Chiang, Hsu, Shang-Te Danny
Source:
Journal of molecular biology 2019 v.431 no.4 pp. 857-863
ISSN:
0022-2836
Subject:
Gibbs free energy, RNA, ligands, methyltransferases, polypeptides, protein conformation, proteins, selection pressure, topology
Abstract:
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.
Agid:
6289461