Stabilization of globular proteins via introduction of temperature-activated elastin-based switches.
To investigate whether swapping native turns of a globular protein with an elastin-based turn sequence (VPGVG) can increase its thermostability, we have performed molecular dynamics simulations of wild-type chymotrypsin inhibitor 2 (CI2) and variants containing elastin-based turns at 10 degrees C and 40 degrees C. Wild-type CI2 is more stable at 10 degrees C, while both of the variant forms are more stable at 40 degrees C. Detailed analyses indicate that the elastin-based turns do indeed contribute to the inverse temperature behavior of the modified proteins. Therefore, swapping a wild-type turn sequence with an elastin-based turn provides a novel way to both improve stability of target proteins at body temperature and to possibly introduce a temperature-sensitive switch.
Department of Medicinal Chemistry, University of Washington, Seattle 98195, USA.
Bin
B
Li
Darwin O V
DO
Alonso
Valerie
V
Daggett
D004549:Elastin / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D010940:Plant Proteins; D017433:Protein Structure, Secondary; D013696:Temperature
D010455:Peptides; D010940:Plant Proteins; C093336:chymotrypsin inhibitor 2; D004549:Elastin