Biological complexity: protein double folding (Introduction)

by David Turell , Friday, January 01, 2021, 15:06 (1205 days ago) @ David Turell

Two functions, two folds in some proteins:

https://science.sciencemag.org/content/371/6524/86

"One sequence encoding two structures
Most proteins have stable, folded structures, but there are rare examples of metamorphic proteins that can switch between two different folds that may each have a different function. Dishman et al. investigated the evolution of XCL1, which is a member of the chemokine family that interconverts between the chemokine fold and a second, noncanonical fold that forms dimers. The authors used nuclear magnetic resonance spectroscopy to investigate the structures of inferred evolutionary ancestral sequences. Their results suggest that XCL1 evolved from an ancestor with the chemokine fold and then transitioned to prefer the noncanonical fold before reaching the modern-day metamorphic protein."

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."

Comment: The chemical details are not important to the point this makes. This is a protein which in two different shapes performs tweo different functions. This is obviously pure design, not any form of natural evolution .