Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry

Jennifer Greaves; Kevin R. Munro; Stuart C. Davidson; Matthieu Riviere; Justyna Wojno; Terry K. Smith; Nicholas C.O. Tomkinson; Luke H. Chamberlain

doi:10.1073/pnas.1612254114

Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry

Jennifer Greaves, Kevin R. Munro, Stuart C. Davidson, Matthieu Riviere, Justyna Wojno, Terry K. Smith, Nicholas C.O. Tomkinson, Luke H. Chamberlain

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

46 Downloads (Pure)

Abstract

S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing their transformation into acyl-CoAs and subsequent click chemistry-based detection, to demonstrate that zDHHC enzymes have marked differences in their fatty acid selectivity. This difference in selectivity was apparent even for highly related enzymes, such as zDHHC3 and zDHHC7, which displayed a marked difference in their ability to use C18:0 acyl-CoA as a substrate. Furthermore, we identified isoleucine-182 in transmembrane domain 3 of zDHHC3 as a key determinant in limiting the use of longer chain acyl-CoAs by this enzyme. This study uncovered differences in the fatty acid selectivity profiles of cellular zDHHC enzymes and mapped molecular determinants governing this selectivity.

Original language	English
Pages (from-to)	E1365-E1374
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	8
Early online date	6 Feb 2017
DOIs	https://doi.org/10.1073/pnas.1612254114
Publication status	Published - 21 Feb 2017
Externally published	Yes

Bibliographical note

Copyright © and Moral Rights are retained by the author(s) and/ or other copyright
owners. A copy can be downloaded for personal non-commercial research or study,
without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

Keywords

Acyl CoA
Click chemistry
Palmitoylation
S-acylation
zDHHC enzyme

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1612254114

Post-printAccepted author manuscript, 12 MB

https://strathprints.strath.ac.uk/59287/

Cite this

Greaves, J., Munro, K. R., Davidson, S. C., Riviere, M., Wojno, J., Smith, T. K., Tomkinson, N. C. O., & Chamberlain, L. H. (2017). Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry. Proceedings of the National Academy of Sciences of the United States of America, 114(8), E1365-E1374. Advance online publication. https://doi.org/10.1073/pnas.1612254114

Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry. / Greaves, Jennifer; Munro, Kevin R.; Davidson, Stuart C. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 8, 21.02.2017, p. E1365-E1374.

Research output: Contribution to journal › Article › peer-review

Greaves, J, Munro, KR, Davidson, SC, Riviere, M, Wojno, J, Smith, TK, Tomkinson, NCO & Chamberlain, LH 2017, 'Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 8, pp. E1365-E1374. https://doi.org/10.1073/pnas.1612254114

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Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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Jennifer Greaves, PhD

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Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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Jennifer Greaves, PhD

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