Fold-switching Proteins

TL;DR

Fold-switching proteins can change their structure in response to stimuli, challenging traditional views of fixed protein folds and revealing important biological functions and evolutionary insights.

Contribution

This paper reviews recent progress in understanding fold-switching proteins, highlighting their biological significance and proposing future research directions.

Findings

Fold-switching proteins are evolutionarily conserved and biologically important.

Recent studies have elucidated mechanisms of fold switching.

Fold switching influences cellular processes and adaptation.

Abstract

Globular proteins are expected to assume folds with fixed secondary structures, alpha-helices and beta-sheets. Fold-switching proteins challenge this expectation by remodeling their secondary and/or tertiary structures in response to cellular stimuli. Though these shapeshifting proteins were once thought to be haphazard evolutionary byproducts with little intrinsic biological relevance, recent work has shown that evolution has selected for their dual-folding behavior, which plays critical roles in biological processes across all kingdoms of life. The widening scope of fold switching draws attention to the ways it challenges conventional wisdom, raising fundamental unanswered questions about protein structure, biophysics, and evolution. Here we discuss the progress being made to answer these questions and suggest future directions for the field.