Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17

Abstract A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of growth factors and inflammatory mediators from the cell surface. Its activity has to be turned on which occurs by various stimuli. The active form can be inactivated by a structural change in its ectodomain, related...

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Autores principales:	Sebastian Krossa, Axel J. Scheidig, Joachim Grötzinger, Inken Lorenzen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e0352618ebd453ea2b6906d705d91f7
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spelling	oai:doaj.org-article:8e0352618ebd453ea2b6906d705d91f72021-12-02T15:09:11ZRedundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 1710.1038/s41598-018-19429-42045-2322https://doaj.org/article/8e0352618ebd453ea2b6906d705d91f72018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19429-4https://doaj.org/toc/2045-2322Abstract A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of growth factors and inflammatory mediators from the cell surface. Its activity has to be turned on which occurs by various stimuli. The active form can be inactivated by a structural change in its ectodomain, related to the pattern of the formed disulphide bridges. The switch-off is executed by protein disulfide isomerases (PDIs) that catalyze an isomerization of two disulfide bridges and thereby cause a disulfide switch. We demonstrate that the integrity of the CGHC-motif within the active site of PDIs is indispensable. In particular, no major variation is apparent in the activities of the two catalytic domains of PDIA6. The affinities between PDIA1, PDIA3, PDIA6 and the targeted domain of ADAM17 are all in the nanomolar range and display no significant differences. The redundancy between PDIs and their disulfide switch activity in ectodomains of transmembrane proteins found in vitro appears to be a basic characteristic. However, different PDIs might be required in vivo for disulfide switches in different tissues and under different cellular and physiological situations.Sebastian KrossaAxel J. ScheidigJoachim GrötzingerInken LorenzenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sebastian Krossa Axel J. Scheidig Joachim Grötzinger Inken Lorenzen Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17
description	Abstract A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of growth factors and inflammatory mediators from the cell surface. Its activity has to be turned on which occurs by various stimuli. The active form can be inactivated by a structural change in its ectodomain, related to the pattern of the formed disulphide bridges. The switch-off is executed by protein disulfide isomerases (PDIs) that catalyze an isomerization of two disulfide bridges and thereby cause a disulfide switch. We demonstrate that the integrity of the CGHC-motif within the active site of PDIs is indispensable. In particular, no major variation is apparent in the activities of the two catalytic domains of PDIA6. The affinities between PDIA1, PDIA3, PDIA6 and the targeted domain of ADAM17 are all in the nanomolar range and display no significant differences. The redundancy between PDIs and their disulfide switch activity in ectodomains of transmembrane proteins found in vitro appears to be a basic characteristic. However, different PDIs might be required in vivo for disulfide switches in different tissues and under different cellular and physiological situations.
format	article
author	Sebastian Krossa Axel J. Scheidig Joachim Grötzinger Inken Lorenzen
author_facet	Sebastian Krossa Axel J. Scheidig Joachim Grötzinger Inken Lorenzen
author_sort	Sebastian Krossa
title	Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17
title_short	Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17
title_full	Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17
title_fullStr	Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17
title_full_unstemmed	Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17
title_sort	redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in a disintegrin and metalloprotease 17
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8e0352618ebd453ea2b6906d705d91f7
work_keys_str_mv	AT sebastiankrossa redundancyofproteindisulfideisomerasesinthecatalysisoftheinactivatingdisulfideswitchinadisintegrinandmetalloprotease17 AT axeljscheidig redundancyofproteindisulfideisomerasesinthecatalysisoftheinactivatingdisulfideswitchinadisintegrinandmetalloprotease17 AT joachimgrotzinger redundancyofproteindisulfideisomerasesinthecatalysisoftheinactivatingdisulfideswitchinadisintegrinandmetalloprotease17 AT inkenlorenzen redundancyofproteindisulfideisomerasesinthecatalysisoftheinactivatingdisulfideswitchinadisintegrinandmetalloprotease17
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Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17

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