Cobbaut, M. and McDonald, Neil and Parker, P.J. (2023) Control of atypical PKCι membrane dissociation by tyrosine phosphorylation within a PB1-C1 interdomain interface. Journal of Biological Chemistry 299 (7), ISSN 0021-9258.
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Abstract
Atypical PKCs are cell polarity kinases that operate at the plasma membrane where they function within multiple molecular complexes to contribute to the establishment and maintenance of polarity. In contrast to the classical and novel PKCs, atypical PKCs do not respond to diacylglycerol cues to bind the membrane compartment. Until recently it was not clear how aPKCs are recruited; whether aPKCs can directly interact with membranes or whether they are dependent on other protein interactors to do so. Two recent studies identified the pseudo-substrate region and the C1 domain as direct membrane interaction modules, however their relative importance and coupling are unknown. We combined molecular modelling and functional assays to show that the regulatory module of aPKCι, comprising the PB1 pseudo-substrate and C1 domains, forms a cooperative and spatially continuous invariant membrane interaction platform. Furthermore, we show the coordinated orientation of membrane-binding elements within the regulatory module requires a key PB1-C1 interfacial β-strand (BSL). We show this element contains a highly conserved Tyr residue that can be phosphorylated and that negatively regulates the integrity of the regulatory module, leading to membrane release. We thus expose a novel regulatory mechanism of aPKCι membrane binding and release during cell polarization.
Metadata
Item Type: | Article |
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School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
Depositing User: | Neil Mcdonald |
Date Deposited: | 17 Jul 2023 13:14 |
Last Modified: | 02 Aug 2023 18:20 |
URI: | https://eprints.bbk.ac.uk/id/eprint/50556 |
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