Oligomerization of a symmetric β‐trefoil protein in response to folding nucleus perturbation

We describe the targeted mutation of the carboxyl ‐terminal region of the (internally located) FN of the de novo designed purely‐symmetric β‐trefoil protein Symfoil‐4P. This mutation involves wholesale replacement of a repeating trefoil‐fold motif with a “blade” motif from a β‐propeller protein, and postulated to trap that region of the Symfoil‐4P FN in a nonproductive folding intermediate. The resulting protein (termed “Bladefoil”) is shown to be cooperatively folding, but as a trimeric oligomer. The results illustrate how symmetric protein architectures have potentially diverse folding alternatives available to them, including oligomerization, when preferred pathways are perturbed.

Source: Protein Science - June 23, 2020 Category: Biochemistry Authors: Connie A. Tenorio, Joseph B. Parker, Michael Blaber Tags: ARTICLE Source Type: research