The incorporation of GALA peptide into a protein cage for an acid-inducible molecular switch.
Caged proteins have been utilized as a biological container in a wide range of applications from material science to biomedicine, and GALA peptide has been known to undergo coil-to-helix transition upon the increased acidity. In this study, GALA synthetic peptide is incorporated to cage protein by genetic modification. Our engineered caged scaffold retains intact at the physiological pH but dissociate completely at pH 6.0, and the dissociated subunits are re-assembled simply by neutralization to biological pH. This acid-induced dissociation has the potential as molecular switch in vivo as well as in vitro so that the acid-sensitive caged proteins are applicable to drug delivery system for acidic target sites such as tumor. Since our design depends on the conformational transition of GALA peptide, not on removal of characteristic interface observed only in viral capsid-like protein, non-viral caged proteins can also be engineered to have molecular switching function. Therefore, this design for acid-sensitive scaffold would broaden the width of applications in nanotechnology including biomimetic material synthesis and biomedicine.
Choi
Seung-Hye
SH
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-Gu, Seoul 136-791, South Korea.
Choi
Kuiwon
K
Chan Kwon
Ick
I
Ahn
Hyung Jun
HJ
D005293:Ferritins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D046912:Multiprotein Complexes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
D046912:Multiprotein Complexes; D010455:Peptides; C066951:GALA peptide; D005293:Ferritins