Exploring the Evolutionary History of Kinetic Stability in the α-Lytic Protease Family.

ABSTRACT: In addition to encoding the tertiary fold and stability, the primary sequence of a protein encodes the folding trajectory and kinetic barriers that determine the speed of folding. How these kinetic barriers are encoded is not well understood. Here, we use evolutionary sequence variation in the α-lytic protease (αLP) protein family to probe the relationship between sequence and energy landscape. αLP has an unusual energy landscape: the native state of αLP is not the most thermodynamically favored conformation and, instead, remains folded due to a large kinetic barrier preventing unfolding. To fold, αLP utilizes an N-terminal pro region similar in size to the protease itself that functions as a folding catalyst. Once folded, the pro region is removed, and the native state does not unfold on

SUBMITTER: Nixon CF 

PROVIDER: S-EPMC8174401 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature