Plain, F., Howie, J., Kennedy, J., Brown, E., Shattock, M. J., Fraser, N. J. and Fuller, W. (2020) Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase. Communications Biology, 3, 411. (doi: 10.1038/s42003-020-01145-3) (PMID:32737405) (PMCID:PMC7395175)
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Abstract
Although palmitoylation regulates numerous cellular processes, as yet efforts to manipulate this post-translational modification for therapeutic gain have proved unsuccessful. The Na-pump accessory sub-unit phospholemman (PLM) is palmitoylated by zDHHC5. Here, we show that PLM palmitoylation is facilitated by recruitment of the Na-pump α sub-unit to a specific site on zDHHC5 that contains a juxtamembrane amphipathic helix. Site-specific palmitoylation and GlcNAcylation of this helix increased binding between the Na-pump and zDHHC5, promoting PLM palmitoylation. In contrast, disruption of the zDHHC5-Na-pump interaction with a cell penetrating peptide reduced PLM palmitoylation. Our results suggest that by manipulating the recruitment of specific substrates to particular zDHHC-palmitoyl acyl transferases, the palmitoylation status of individual proteins can be selectively altered, thus opening the door to the development of molecular modulators of protein palmitoylation for the treatment of disease.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Howie, Dr Jacqueline and Fuller, Professor Will and Brown, Miss Elaine |
| Authors: | Plain, F., Howie, J., Kennedy, J., Brown, E., Shattock, M. J., Fraser, N. J., and Fuller, W. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Communications Biology |
| Publisher: | Nature Research |
| ISSN: | 2399-3642 |
| ISSN (Online): | 2399-3642 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Communications Biology 3:411 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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