Folding of a tandemly knotted protein: Evidence that a polypeptide chain can get out of deep kinetic traps.

ABSTRACT: It is hard to imagine how proteins can thread and form knots in their polypeptide chains, but they do. These topologically complex structures have challenged the traditional protein folding views of simple funnel-shaped energy landscapes. Previous experimental studies on the folding mechanisms of deeply knotted proteins with a single trefoil knot have yielded evidence that this topology has a more complicated folding landscape than other simpler proteins. However, to date, there have been no attempts to study the folding of any protein in which multiple threading events are needed to create more than one knot within a single polypeptide chain. Here, we report the construction and characterization of an artificial tandemly knotted protein. We find compelling evidence that both domains of th

SUBMITTER: Zhang H 

PROVIDER: S-EPMC11837048 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature