Translocation of a knotted polypeptide through a pore.
We use Langevin dynamics simulations to study how the presence of a deep knot affects the time it takes to thread a polypeptide chain through a narrow pore by pulling mechanically at its end. The polypeptide was designed to contain a knotted unstructured segment inserted between two beta-hairpins, which prevented the knot from slipping off the chain ends. In the range of forces studied (40-200 pN), the mean translocation time increased with the knot complexity. The type 5(2) knot, which was recently discovered in the structure of human ubiquitin hydrolase and is the most complex knot found in the protein databank, slows down translocation by about two orders of magnitude, as compared to the unknotted chain. In contrast to the unknotted chain case, the translocation mechanism of knotted chains involves multiple slippage events suggesting that the corresponding free energy landscape is rugged and involves multiple metastable minima.
Huang
Lei
L
Department of Chemistry and Biochemistry and Institute for Theoretical Chemistry, University of Texas at Austin, Austin, Texas 78712, USA.
Makarov
Dmitrii E
DE
D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D016062:Porosity; D011487:Protein Conformation; D013997:Time Factors
D010455:Peptides