Year: 2026
Type: review
Abstract: Shape-shifting proteins include intrinsically disordered proteins (IDPs) and fold-switching, or metamorphic proteins. They make up a significant fraction of the "dark proteome" in the protein universe. In this essay, we highlight some often misconceived or underappreciated features of shape-shifting proteins: First, the subtlety of the structure of IDPs; second, the relationship between intrinsic disorder and allostery, third, the possibility of discerning IDP conformational preferences based on energy landscape theory, and fourth, the contributions of disordered regions to fold switching in metamorphic proteins. Lastly, we highlight emerging evidence that fold-switching/metamorphic proteins may contribute to phenotypic plasticity and adaptive evolution by acting as evolutionary capacitors.
Source: iScience
Institutions: California Institute of Technology, City Of Hope National Medical Center, City of Hope, Beckman Research Institute, Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, University of South Florida, North Carolina State University, Institute for Systems Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Award: Cancer Center Support Grant
OpenAlex ID: W7211933143