Design of a pH-dependent molecular switch in a caged protein platform.
Self-assembling protein cages provide a wide range of possible applications in nanotechnology. We report the first example of an engineered pH-dependent molecular switch in a virus-like particle. By genetically manipulating the subunit-subunit interface of the E2 subunit of pyruvate dehydrogenase, we introduce pH-responsive assembly into a scaffold that is natively stable at both pH 5.0 and 7.4. The redesigned protein module yields an intact, stable particle at pH 7.4 that dissociates at pH 5.0. This triggered behavior is especially relevant for applications in therapeutic delivery.
Dalmau
Mercè
M
Department of Chemical Engineering and Materials Science, University of California, Irvine, California 92697-2575, USA.
Lim
Sierin
S
Wang
Szu-Wen
SW
D003460:Crystallization / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D015202:Protein Engineering / Q000379:methods*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics
D004337:Drug Carriers; D014759:Viral Envelope Proteins