Global, site-specific analysis of neuronal protein S-acylation

Abstract Protein S-acylation (palmitoylation) is a reversible lipid modification that is an important regulator of dynamic membrane-protein interactions. Proteomic approaches have uncovered many putative palmitoylated proteins however, methods for comprehensive palmitoylation site characterization a...

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Autores principales:	Mark O. Collins, Keith T. Woodley, Jyoti S. Choudhary
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4252b6aecd944ee38ded21a9281f9cf3
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spelling	oai:doaj.org-article:4252b6aecd944ee38ded21a9281f9cf32021-12-02T12:32:50ZGlobal, site-specific analysis of neuronal protein S-acylation10.1038/s41598-017-04580-12045-2322https://doaj.org/article/4252b6aecd944ee38ded21a9281f9cf32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04580-1https://doaj.org/toc/2045-2322Abstract Protein S-acylation (palmitoylation) is a reversible lipid modification that is an important regulator of dynamic membrane-protein interactions. Proteomic approaches have uncovered many putative palmitoylated proteins however, methods for comprehensive palmitoylation site characterization are lacking. We demonstrate a quantitative site-specific-Acyl-Biotin-Exchange (ssABE) method that allowed the identification of 906 putative palmitoylation sites on 641 proteins from mouse forebrain. 62% of sites map to known palmitoylated proteins and 102 individual palmitoylation sites are known from the literature. 54% of palmitoylation sites map to synaptic proteins including many GPCRs, receptors/ion channels and peripheral membrane proteins. Phosphorylation sites were also identified on a subset of peptides that were palmitoylated, demonstrating for the first time co-identification of these modifications by mass spectrometry. Palmitoylation sites were identified on over half of the family of palmitoyl-acyltransferases (PATs) that mediate protein palmitoylation, including active site thioester-linked palmitoyl intermediates. Distinct palmitoylation motifs and site topology were identified for integral membrane and soluble proteins, indicating potential differences in associated PAT specificity and palmitoylation function. ssABE allows the global identification of palmitoylation sites as well as measurement of the active site modification state of PATs, enabling palmitoylation to be studied at a systems level.Mark O. CollinsKeith T. WoodleyJyoti S. ChoudharyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mark O. Collins Keith T. Woodley Jyoti S. Choudhary Global, site-specific analysis of neuronal protein S-acylation
description	Abstract Protein S-acylation (palmitoylation) is a reversible lipid modification that is an important regulator of dynamic membrane-protein interactions. Proteomic approaches have uncovered many putative palmitoylated proteins however, methods for comprehensive palmitoylation site characterization are lacking. We demonstrate a quantitative site-specific-Acyl-Biotin-Exchange (ssABE) method that allowed the identification of 906 putative palmitoylation sites on 641 proteins from mouse forebrain. 62% of sites map to known palmitoylated proteins and 102 individual palmitoylation sites are known from the literature. 54% of palmitoylation sites map to synaptic proteins including many GPCRs, receptors/ion channels and peripheral membrane proteins. Phosphorylation sites were also identified on a subset of peptides that were palmitoylated, demonstrating for the first time co-identification of these modifications by mass spectrometry. Palmitoylation sites were identified on over half of the family of palmitoyl-acyltransferases (PATs) that mediate protein palmitoylation, including active site thioester-linked palmitoyl intermediates. Distinct palmitoylation motifs and site topology were identified for integral membrane and soluble proteins, indicating potential differences in associated PAT specificity and palmitoylation function. ssABE allows the global identification of palmitoylation sites as well as measurement of the active site modification state of PATs, enabling palmitoylation to be studied at a systems level.
format	article
author	Mark O. Collins Keith T. Woodley Jyoti S. Choudhary
author_facet	Mark O. Collins Keith T. Woodley Jyoti S. Choudhary
author_sort	Mark O. Collins
title	Global, site-specific analysis of neuronal protein S-acylation
title_short	Global, site-specific analysis of neuronal protein S-acylation
title_full	Global, site-specific analysis of neuronal protein S-acylation
title_fullStr	Global, site-specific analysis of neuronal protein S-acylation
title_full_unstemmed	Global, site-specific analysis of neuronal protein S-acylation
title_sort	global, site-specific analysis of neuronal protein s-acylation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4252b6aecd944ee38ded21a9281f9cf3
work_keys_str_mv	AT markocollins globalsitespecificanalysisofneuronalproteinsacylation AT keithtwoodley globalsitespecificanalysisofneuronalproteinsacylation AT jyotischoudhary globalsitespecificanalysisofneuronalproteinsacylation
_version_	1718393912434884608

Global, site-specific analysis of neuronal protein S-acylation

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