Minimally disruptive optical control of protein tyrosine phosphatase 1B

Akarawin Hongdusit, Peter H. Zwart, Banumathi Sankaran, and Jerome M. Fox

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Sep 20, 2019
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Received Date: 10th September 19

Protein tyrosine phosphatases regulate a myriad of essential subcellular signaling events, yet they remain difficult to study in their native biophysical context. Here we develop a minimally disruptive optical approach to toggle the activity of protein tyrosine phosphatase 1B (PTP1B)—an important regulator of receptor tyrosine kinases and a therapeutic target for the treatment of diabetes, obesity, and cancer—and we use that approach to probe both the structure and intracellular function of this enzyme. Our conservative architecture for photocontrol, which consists of a protein-based light switch fused to an allosteric regulatory element, preserves the native structure, activity, and subcellular localization of PTP1B, affords changes in activity that match those elicited by post-translational modifications inside the cell, and permits experimental analyses of the molecular basis of optical modulation. This work provides a framework for using optogenetic systems to examine both the biophysical basis and spatial context of cell signaling.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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