Protein knotting through concatenation significantly reduces folding stability.

ABSTRACT: Concatenation by covalent linkage of two protomers of an intertwined all-helical HP0242 homodimer from Helicobacter pylori results in the first example of an engineered knotted protein. While concatenation does not affect the native structure according to X-ray crystallography, the folding kinetics is substantially slower compared to the parent homodimer. Using NMR hydrogen-deuterium exchange analysis, we showed here that concatenation destabilises significantly the knotted structure in solution, with some regions close to the covalent linkage being destabilised by as much as 5 kcal mol^-1. Structural mapping of chemical shift perturbations induced by concatenation revealed a pattern that is similar to the effect induced by concentrated chaotrophic agent. Our results suggested th

SUBMITTER: Hsu SD 

PROVIDER: S-EPMC5159899 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature