Rational design of heterodimeric receptors capable of activating target signaling molecules

Abstract Intracellular signal transduction is regulated by a variety of transmembrane receptors. Many researchers have aimed to arbitrarily regulate the intracellular signaling and subsequent cell fate with artificial receptors, of which the ligand recognition and signaling properties could be artif...

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Autores principales:	Tatphon Kongkrongtong, Ruolan Zhang, Masahiro Kawahara
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78786056a6fb4a36a6c43e8b6e9ea6e9
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spelling	oai:doaj.org-article:78786056a6fb4a36a6c43e8b6e9ea6e92021-12-02T17:08:24ZRational design of heterodimeric receptors capable of activating target signaling molecules10.1038/s41598-021-96396-32045-2322https://doaj.org/article/78786056a6fb4a36a6c43e8b6e9ea6e92021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96396-3https://doaj.org/toc/2045-2322Abstract Intracellular signal transduction is regulated by a variety of transmembrane receptors. Many researchers have aimed to arbitrarily regulate the intracellular signaling and subsequent cell fate with artificial receptors, of which the ligand recognition and signaling properties could be artificially designed. Although several architectures of homodimeric artificial receptors have been reported, engineering of heterodimeric receptors, which are abundant among natural receptors, have yet to be thoroughly investigated. In this study, we rationally design artificial heterodimeric receptors for activating target signaling molecules. We locate a tyrosine motif on an engineered tyrosine kinase domain, which is further connected to a small molecule-responsive heterodimeric module, attaining a pair of heterodimeric receptors with different tyrosine motifs within the pair. The resultant heterodimeric receptors successfully activate target signaling molecules and even control cell proliferation levels according to the properties of tyrosine motifs connected. Thus, our heterodimeric receptors may open a new era of tailor-made designer receptors, which could be useful for cell therapy against intractable diseases.Tatphon KongkrongtongRuolan ZhangMasahiro KawaharaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tatphon Kongkrongtong Ruolan Zhang Masahiro Kawahara Rational design of heterodimeric receptors capable of activating target signaling molecules
description	Abstract Intracellular signal transduction is regulated by a variety of transmembrane receptors. Many researchers have aimed to arbitrarily regulate the intracellular signaling and subsequent cell fate with artificial receptors, of which the ligand recognition and signaling properties could be artificially designed. Although several architectures of homodimeric artificial receptors have been reported, engineering of heterodimeric receptors, which are abundant among natural receptors, have yet to be thoroughly investigated. In this study, we rationally design artificial heterodimeric receptors for activating target signaling molecules. We locate a tyrosine motif on an engineered tyrosine kinase domain, which is further connected to a small molecule-responsive heterodimeric module, attaining a pair of heterodimeric receptors with different tyrosine motifs within the pair. The resultant heterodimeric receptors successfully activate target signaling molecules and even control cell proliferation levels according to the properties of tyrosine motifs connected. Thus, our heterodimeric receptors may open a new era of tailor-made designer receptors, which could be useful for cell therapy against intractable diseases.
format	article
author	Tatphon Kongkrongtong Ruolan Zhang Masahiro Kawahara
author_facet	Tatphon Kongkrongtong Ruolan Zhang Masahiro Kawahara
author_sort	Tatphon Kongkrongtong
title	Rational design of heterodimeric receptors capable of activating target signaling molecules
title_short	Rational design of heterodimeric receptors capable of activating target signaling molecules
title_full	Rational design of heterodimeric receptors capable of activating target signaling molecules
title_fullStr	Rational design of heterodimeric receptors capable of activating target signaling molecules
title_full_unstemmed	Rational design of heterodimeric receptors capable of activating target signaling molecules
title_sort	rational design of heterodimeric receptors capable of activating target signaling molecules
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/78786056a6fb4a36a6c43e8b6e9ea6e9
work_keys_str_mv	AT tatphonkongkrongtong rationaldesignofheterodimericreceptorscapableofactivatingtargetsignalingmolecules AT ruolanzhang rationaldesignofheterodimericreceptorscapableofactivatingtargetsignalingmolecules AT masahirokawahara rationaldesignofheterodimericreceptorscapableofactivatingtargetsignalingmolecules
_version_	1718381560640569344

Rational design of heterodimeric receptors capable of activating target signaling molecules

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