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Modular Thermal Control of Protein Dimerization

Piraner, Dan I. and Wu, Yan and Shapiro, Mikhail G. (2019) Modular Thermal Control of Protein Dimerization. . (Unpublished) http://resolver.caltech.edu/CaltechAUTHORS:20190716-114821416

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Abstract

Protein-protein interactions and protein localization are essential mechanisms of cellular signal transduction. The ability to externally control such interactions using chemical and optogenetic methods has facilitated biological research and provided components for the engineering of cell-based therapies and materials. However, chemical and optical methods are limited in their ability to provide spatiotemporal specificity in light-scattering tissues. To overcome these limitations, we present “thermomers,” modular protein dimerization domains controlled with temperature – a form of energy that can be delivered to cells both globally and locally in a wide variety of in vitro and in vivo contexts. Thermomers are based on a sharply thermolabile coiled-coil protein, which we engineered to heterodimerize at a tunable transition temperature within the biocompatible range of 37–42 °C. When fused to other proteins, thermomers can reversibly control their association, as demonstrated via membrane localization in mammalian cells. This technology enables remote control of intracellular protein-protein interactions with a form of energy that can be delivered with spatiotemporal precision in a wide range of biological, therapeutic and living material scenarios.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/694448DOIDiscussion Paper
ORCID:
AuthorORCID
Piraner, Dan I.0000-0003-3857-9487
Shapiro, Mikhail G.0000-0002-0291-4215
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Jul. 13, 2019. The authors thank Mohamad Abedi and Andres Collazo for helpful discussions. Microscopy was performed at the Biological Imaging Facility of the Beckman Institute at Caltech. This research was supported by the Defense Advanced Research Projects Agency (D14AP0050), the Sontag Foundation and the Army Institute for Collaborative Biotechnologies (W911NF-19-D-0001). D.I.P. was supported by the NIH fellowship for Predoctoral Training in Biology and Chemistry (T32GM007616).
Funders:
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)D14AP0050
Sontag FoundationUNSPECIFIED
Army Research Office (ARO)W911NF-19-D-0001
NIH Predoctoral FellowshipT32GM007616
Record Number:CaltechAUTHORS:20190716-114821416
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190716-114821416
Official Citation:Modular Thermal Control of Protein Dimerization. Dan I. Piraner, Yan Wu, Mikhail G. Shapiro. bioRxiv 694448; doi: https://doi.org/10.1101/694448
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:97175
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 Jul 2019 18:53
Last Modified:16 Jul 2019 18:53

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