Evolution and Functional Advantages of Protein Metamorphosis

Abstract

Metamorphic proteins adopt two or more different native folds, expanding the protein folding paradigm. Initially viewed as an anomaly, numerous analyses suggest that metamorphic proteins may be more common than expected. The chemokine XCL1 is a metamorphic protein that spontaneously, reversibly interconverts between two distinct structures (an all β-sheet dimer and the α-β chemokine structure) and exhibits antibacterial activity. Here, we investigate the emergence of XCL1's metamorphosis using ancestral reconstruction, biophysical characterization, and bioinformatic analysis.