Evolution of fold switching in a metamorphic protein
Year: 2020
Type: article
Abstract: Metamorphic proteins switch between different folds, defying the protein folding paradigm. It is unclear how fold switching arises during evolution. With ancestral reconstruction and nuclear magnetic resonance, we studied the evolution of the metamorphic human protein XCL1, which has two distinct folds with different functions, making it an unusual member of the chemokine family, whose members generally adopt one conserved fold. XCL1 evolved from an ancestor with the chemokine fold. Evolution of a dimer interface, changes in structural constraints and molecular strain, and alteration of intramolecular protein contacts drove the evolution of metamorphosis. Then, XCL1 likely evolved to preferentially populate the noncanonical fold before reaching its modern-day near-equal population of folds. These discoveries illuminate how one sequence has evolved to encode multiple structures, revealing principles for protein design and engineering.
Source: Science
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: American Lebanese Syrian Associated Charities, Novo Nordisk Fonden, National Institutes of Health, Medical College of Wisconsin Cancer Center, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W3117945779