The Jackson Laboratory Research: Protein Folding

Stability and folding studies of Ubiquitin in the cellular environment.

Ubiquitin is a 76 residue β-grasp globular protein present in all eukaryotes; it is highly conserved from yeast to plants to mankind and is involved in vast numbers of cellular processes. Its principal function is to mark other peptides for destruction by the proteasome, regulating the quantity of key proteins in the cytoplasm.

We have been investigating the folding pathway of ubiquitin for several years using protein engineering techniques. Previous research has been concerned with mapping out the pathway of folding of ubiquitin by quantitiatively measuring the interactions that are present in the main folding transition state in vitro. We are currently working on the comparative stability of ubiquitin in vivo by simulating the environment of the cell in vitro using macromolecular crowding agents and looking at the stability of the protein inside live yeast cells. These investigations encompass a variety of techniques from SUPEREX mass-spectrometry, stopped-flow kinetics, in vitro/in vivo equilibrium denaturation and a number of molecular biological experiments. The overall aim is to elucidate how the stability and folding pathway of this model protein is affected by its natural environment.

Leading References

  • Roberts A, Jackson SE (2007)"Destabilised mutants of ubiquitin gain equal stability in crowded solutions." Biophys. Chem. 128(2-3):140-149. PDF

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