Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style

Tianlu Wang; Lian He; Ji Jing; Tien Hung Lan; Tingting Hong; Fen Wang; Yun Huang; Guolin Ma; Yubin Zhou

doi:10.1002/advs.202002148

Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style

Tianlu Wang, Lian He, Ji Jing, Tien Hung Lan, Tingting Hong, Fen Wang, Yun Huang, Guolin Ma, Yubin Zhou

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Further rationalized engineering of COSMO leads to 34–217-fold enhancement in caffeine sensitivity (EC₅₀ = 16.9 nanomolar), which makes it among the most potent CID systems like the FK506 binding protein (FKBP)–FKBP rapamycin binding domain (FRB)–rapamycin complex. Furthermore, bivalent COSMO (biCOMSO) connected with a long linker favors intramolecular dimerization and acts as a versatile precision switch when inserted in host proteins to achieve tailored function. Given the modularity and high transferability of COMSO and biCOSMO, these chemical biology tools are anticipated to greatly accelerate the development of therapeutic cells and biologics that can be switched on and off by caffeinated beverages commonly consumed in the daily life.

Original language	English (US)
Article number	2002148
Pages (from-to)	2002148
Journal	Advanced Science
Volume	8
Issue number	3
DOIs	https://doi.org/10.1002/advs.202002148
State	Published - Feb 3 2021

Keywords

SARS-Cov-2
allosteric switch
caffeine
chemical biology
chemically induced dimerization
nanobody

ASJC Scopus subject areas

Medicine (miscellaneous)
General Chemical Engineering
General Materials Science
Biochemistry, Genetics and Molecular Biology (miscellaneous)
General Engineering
General Physics and Astronomy

Access to Document

10.1002/advs.202002148

Cite this

@article{118017e13b814df4bfcf58af127777b5,

title = "Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style",

abstract = "A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Further rationalized engineering of COSMO leads to 34–217-fold enhancement in caffeine sensitivity (EC50 = 16.9 nanomolar), which makes it among the most potent CID systems like the FK506 binding protein (FKBP)–FKBP rapamycin binding domain (FRB)–rapamycin complex. Furthermore, bivalent COSMO (biCOMSO) connected with a long linker favors intramolecular dimerization and acts as a versatile precision switch when inserted in host proteins to achieve tailored function. Given the modularity and high transferability of COMSO and biCOSMO, these chemical biology tools are anticipated to greatly accelerate the development of therapeutic cells and biologics that can be switched on and off by caffeinated beverages commonly consumed in the daily life.",

keywords = "SARS-Cov-2, allosteric switch, caffeine, chemical biology, chemically induced dimerization, nanobody",

author = "Tianlu Wang and Lian He and Ji Jing and Lan, {Tien Hung} and Tingting Hong and Fen Wang and Yun Huang and Guolin Ma and Yubin Zhou",

note = "Funding Information: T.W. and L.H. contributed equally to this work. The authors thank the financial supports from the National Institutes of Health (R01GM112003 to Y.Z., R21GM126532 and R01CA232017 to Y.Z., R01HL134780 to Y.H., and R01HL146852 to Y.H.), the Welch Foundation (BE‐1913‐20190330 to Y.Z.), the John S. Dunn Foundation (to Y.Z.), the Cancer Prevention and Research Institutes of Texas (RP190612 to F.W.), and the American Cancer Society (RSG‐16‐215‐01‐TBE to Y.Z. and RSG‐18‐043‐01‐LIB to Y.H.). Funding Information: T.W. and L.H. contributed equally to this work. The authors thank the financial supports from the National Institutes of Health (R01GM112003 to Y.Z., R21GM126532 and R01CA232017 to Y.Z., R01HL134780 to Y.H., and R01HL146852 to Y.H.), the Welch Foundation (BE-1913-20190330 to Y.Z.), the John S. Dunn Foundation (to Y.Z.), the Cancer Prevention and Research Institutes of Texas (RP190612 to F.W.), and the American Cancer Society (RSG-16-215-01-TBE to Y.Z. and RSG-18-043-01-LIB to Y.H.). Publisher Copyright: {\textcopyright} 2020 The Authors. Published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

day = "3",

doi = "10.1002/advs.202002148",

language = "English (US)",

volume = "8",

pages = "2002148",

journal = "Advanced Science",

issn = "2198-3844",

publisher = "Wiley",

number = "3",

}

TY - JOUR

T1 - Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style

AU - Wang, Tianlu

AU - He, Lian

AU - Jing, Ji

AU - Lan, Tien Hung

AU - Hong, Tingting

AU - Wang, Fen

AU - Huang, Yun

AU - Ma, Guolin

AU - Zhou, Yubin

N1 - Funding Information: T.W. and L.H. contributed equally to this work. The authors thank the financial supports from the National Institutes of Health (R01GM112003 to Y.Z., R21GM126532 and R01CA232017 to Y.Z., R01HL134780 to Y.H., and R01HL146852 to Y.H.), the Welch Foundation (BE‐1913‐20190330 to Y.Z.), the John S. Dunn Foundation (to Y.Z.), the Cancer Prevention and Research Institutes of Texas (RP190612 to F.W.), and the American Cancer Society (RSG‐16‐215‐01‐TBE to Y.Z. and RSG‐18‐043‐01‐LIB to Y.H.). Funding Information: T.W. and L.H. contributed equally to this work. The authors thank the financial supports from the National Institutes of Health (R01GM112003 to Y.Z., R21GM126532 and R01CA232017 to Y.Z., R01HL134780 to Y.H., and R01HL146852 to Y.H.), the Welch Foundation (BE-1913-20190330 to Y.Z.), the John S. Dunn Foundation (to Y.Z.), the Cancer Prevention and Research Institutes of Texas (RP190612 to F.W.), and the American Cancer Society (RSG-16-215-01-TBE to Y.Z. and RSG-18-043-01-LIB to Y.H.). Publisher Copyright: © 2020 The Authors. Published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/3

Y1 - 2021/2/3

N2 - A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Further rationalized engineering of COSMO leads to 34–217-fold enhancement in caffeine sensitivity (EC50 = 16.9 nanomolar), which makes it among the most potent CID systems like the FK506 binding protein (FKBP)–FKBP rapamycin binding domain (FRB)–rapamycin complex. Furthermore, bivalent COSMO (biCOMSO) connected with a long linker favors intramolecular dimerization and acts as a versatile precision switch when inserted in host proteins to achieve tailored function. Given the modularity and high transferability of COMSO and biCOSMO, these chemical biology tools are anticipated to greatly accelerate the development of therapeutic cells and biologics that can be switched on and off by caffeinated beverages commonly consumed in the daily life.

AB - A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Further rationalized engineering of COSMO leads to 34–217-fold enhancement in caffeine sensitivity (EC50 = 16.9 nanomolar), which makes it among the most potent CID systems like the FK506 binding protein (FKBP)–FKBP rapamycin binding domain (FRB)–rapamycin complex. Furthermore, bivalent COSMO (biCOMSO) connected with a long linker favors intramolecular dimerization and acts as a versatile precision switch when inserted in host proteins to achieve tailored function. Given the modularity and high transferability of COMSO and biCOSMO, these chemical biology tools are anticipated to greatly accelerate the development of therapeutic cells and biologics that can be switched on and off by caffeinated beverages commonly consumed in the daily life.

KW - SARS-Cov-2

KW - allosteric switch

KW - caffeine

KW - chemical biology

KW - chemically induced dimerization

KW - nanobody

UR - http://www.scopus.com/inward/record.url?scp=85097497247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85097497247&partnerID=8YFLogxK

U2 - 10.1002/advs.202002148

DO - 10.1002/advs.202002148

M3 - Article

C2 - 33552855

AN - SCOPUS:85097497247

SN - 2198-3844

VL - 8

SP - 2002148

JO - Advanced Science

JF - Advanced Science

IS - 3

M1 - 2002148

ER -

Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this