Mimicking cAMP-dependent allosteric control of protein kinase A through mechanical tension.
We report the activation of an enzyme complex by mechanical tension. Protein kinase A, a tetrameric enzyme that, in the cell, is allosterically controlled by cAMP, has been modified by the insertion of a "molecular spring" on the regulatory subunit. The spring is made of DNA, and its stiffness can be varied externally by hybridization to a complementary strand. This allows us to exert a controlled mechanical tension between the two points on the protein's surface where the spring is attached. We show that upon applying the tension, we can activate the enzyme with efficiency comparable to the activation by its natural regulatory molecule, cAMP.
Choi
Brian
B
Department of Physics and Astronomy, University of California-Los Angeles, Los Angeles, CA 90095-1547, USA.
Zocchi
Giovanni
G
D000494:Allosteric Regulation; D000242:Cyclic AMP / Q000737:chemistry*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000302:isolation & purification; D004247:DNA / Q000737:chemistry; D004789:Enzyme Activation; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship
D004247:DNA; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases