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Transmembrane signal transduction by cofactor transport

Information processing and cell signalling in biological systems relies on passing chemical signals across lipid bilayer membranes, but examples of synthetic systems that can achieve this process are rare. A synthetic transducer has been developed that triggers catalytic hydrolysis of an ester subst...

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Detalles Bibliográficos
Autores principales: Kocsis, Istvan, Ding, Yudi, Williams, Nicholas H., Hunter, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480319/
https://www.ncbi.nlm.nih.gov/pubmed/34603667
http://dx.doi.org/10.1039/d1sc03910e
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author Kocsis, Istvan
Ding, Yudi
Williams, Nicholas H.
Hunter, Christopher A.
author_facet Kocsis, Istvan
Ding, Yudi
Williams, Nicholas H.
Hunter, Christopher A.
author_sort Kocsis, Istvan
collection PubMed
description Information processing and cell signalling in biological systems relies on passing chemical signals across lipid bilayer membranes, but examples of synthetic systems that can achieve this process are rare. A synthetic transducer has been developed that triggers catalytic hydrolysis of an ester substrate inside lipid vesicles in response to addition of metal ions to the external vesicle solution. The output signal generated in the internal compartment of the vesicles is produced by binding of a metal ion cofactor to a head group on the transducer to form a catalytically competent complex. The mechanism of signal transduction is based on transport of the metal ion cofactor across the bilayer by the transducer, and the system can be reversibly switched between on and off states by adding cadmium(ii) and ethylene diamine tetracarboxylic acid input signals respectively. The transducer is also equipped with a hydrazide moiety, which allows modulation of activity through covalent conjugation with aldehydes. Conjugation with a sugar derivative abolished activity, because the resulting hydrazone is too polar to cross the bilayer, whereas conjugation with a pyridine derivative increased activity. Coupling transport with catalysis provides a straightforward mechanism for generating complex systems using simple components.
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spelling pubmed-84803192021-10-01 Transmembrane signal transduction by cofactor transport Kocsis, Istvan Ding, Yudi Williams, Nicholas H. Hunter, Christopher A. Chem Sci Chemistry Information processing and cell signalling in biological systems relies on passing chemical signals across lipid bilayer membranes, but examples of synthetic systems that can achieve this process are rare. A synthetic transducer has been developed that triggers catalytic hydrolysis of an ester substrate inside lipid vesicles in response to addition of metal ions to the external vesicle solution. The output signal generated in the internal compartment of the vesicles is produced by binding of a metal ion cofactor to a head group on the transducer to form a catalytically competent complex. The mechanism of signal transduction is based on transport of the metal ion cofactor across the bilayer by the transducer, and the system can be reversibly switched between on and off states by adding cadmium(ii) and ethylene diamine tetracarboxylic acid input signals respectively. The transducer is also equipped with a hydrazide moiety, which allows modulation of activity through covalent conjugation with aldehydes. Conjugation with a sugar derivative abolished activity, because the resulting hydrazone is too polar to cross the bilayer, whereas conjugation with a pyridine derivative increased activity. Coupling transport with catalysis provides a straightforward mechanism for generating complex systems using simple components. The Royal Society of Chemistry 2021-08-20 /pmc/articles/PMC8480319/ /pubmed/34603667 http://dx.doi.org/10.1039/d1sc03910e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Kocsis, Istvan
Ding, Yudi
Williams, Nicholas H.
Hunter, Christopher A.
Transmembrane signal transduction by cofactor transport
title Transmembrane signal transduction by cofactor transport
title_full Transmembrane signal transduction by cofactor transport
title_fullStr Transmembrane signal transduction by cofactor transport
title_full_unstemmed Transmembrane signal transduction by cofactor transport
title_short Transmembrane signal transduction by cofactor transport
title_sort transmembrane signal transduction by cofactor transport
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480319/
https://www.ncbi.nlm.nih.gov/pubmed/34603667
http://dx.doi.org/10.1039/d1sc03910e
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