Controlling Optical and Catalytic Activity of Genetically Engineered Proteins by Ultrasound. Issue 3 (13th November 2020)

• Record Type: Journal Article
• Authors: Zhou, Yu; Huo, Shuaidong; Loznik, Mark; Göstl, Robert; Boersma, Arnold J.; Herrmann, Andreas
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 3(2021)
• Page Start: 1493
• Page End: 1497
• Publication Date: 2020-11-13
• Subjects: enzymes -- fluorescence -- mechanochemistry -- protein engineering -- ultrasound; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202010324
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Ultrasound (US) produces cavitation‐induced mechanical forces stretching and breaking polymer chains in solution. This type of polymer mechanochemistry is widely used for synthetic polymers, but not biomacromolecules, even though US is biocompatible and commonly used for medical therapy as well as in vivo imaging. The ability to control protein activity by US would thus be a major stepping‐stone for these disciplines. Here, we provide the first examples of selective protein activation and deactivation by means of US. Using GFP as a model system, we engineer US sensitivity into proteins by design. The incorporation of long and highly charged domains enables the efficient transfer of force to the protein structure. We then use this principle to activate the catalytic activity of trypsin by inducing the release of its inhibitor. We expect that this concept to switch "on" and "off" protein activity by US will serve as a blueprint to remotely control other bioactive molecules. Abstract : Proteins are genetically engineered and equipped with long supercharged polypeptide handles, rendering them susceptible to ultrasound. The concept is demonstrated by designing ultrasound‐responsive GFP derivatives the fluorescence of which can be switched "off, " while the activation of catalytic activity is switched "on" by ultrasound using trypsin in conjunction with a protein inhibitor.