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dc.contributor.authorTay, CLen_US
dc.contributor.authorJones, MLen_US
dc.contributor.authorHodson, Nen_US
dc.contributor.authorTheron, Men_US
dc.contributor.authorChoudhary, JSen_US
dc.contributor.authorRayner, JCen_US
dc.date.accessioned2020-10-16T09:28:40Z
dc.date.issued2016-11en_US
dc.identifier.citationCellular microbiology, 2016, 18 (11), pp. 1596 - 1610en_US
dc.identifier.issn1462-5814en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4172
dc.identifier.eissn1462-5822en_US
dc.identifier.doi10.1111/cmi.12599en_US
dc.description.abstractPalmitoylation is the post-translational reversible addition of the acyl moiety, palmitate, to cysteine residues of proteins and is involved in regulating protein trafficking, localization, stability and function. The Aspartate-Histidine-Histidine-Cysteine (DHHC) protein family, named for their highly conserved DHHC signature motif, is thought to be responsible for catalysing protein palmitoylation. Palmitoylation is widespread in all eukaryotes, including the malaria parasite, Plasmodium falciparum, where over 400 palmitoylated proteins are present in the asexual intraerythrocytic schizont stage parasites, including proteins involved in key aspects of parasite maturation and development. The P. falciparum genome includes 12 proteins containing the conserved DHHC motif. In this study, we adapted a palmitoyl-transferase activity assay for use with P. falciparum proteins and demonstrated for the first time that P. falciparum DHHC proteins are responsible for the palmitoylation of P. falciparum substrates. This assay also reveals that multiple DHHCs are capable of palmitoylating the same substrate, indicating functional redundancy at least in vitro. To test whether functional redundancy also exists in vivo, we investigated the endogenous localization and essentiality of a subset of schizont-expressed PfDHHC proteins. Individual PfDHHC proteins localized to distinct organelles, including parasite-specific organelles such as the rhoptries and inner membrane complex. Knock-out studies identified individual DHHCs that may be essential for blood-stage growth and others that were functionally redundant in the blood stages but may have functions in other stages of parasite development. Supporting this hypothesis, disruption of PfDHHC9 had no effect on blood-stage growth but reduced the formation of gametocytes, suggesting that this protein could be exploited as a transmission-blocking target. The localization and stage-specific expression of the DHHC proteins may be important for regulating their substrate specificity and thus may provide a path for inhibitor development.en_US
dc.formatPrint-Electronicen_US
dc.format.extent1596 - 1610en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectErythrocytesen_US
dc.subjectHumansen_US
dc.subjectPlasmodium falciparumen_US
dc.subjectAcyltransferasesen_US
dc.subjectPalmitic Aciden_US
dc.subjectProtozoan Proteinsen_US
dc.subjectProtein Processing, Post-Translationalen_US
dc.subjectAmino Acid Sequenceen_US
dc.subjectSubstrate Specificityen_US
dc.subjectSchizontsen_US
dc.subjectLipoylationen_US
dc.subjectHEK293 Cellsen_US
dc.titleStudy of Plasmodium falciparum DHHC palmitoyl transferases identifies a role for PfDHHC9 in gametocytogenesis.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-03-29en_US
rioxxterms.versionofrecord10.1111/cmi.12599en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2016-11en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCellular microbiologyen_US
pubs.issue11en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.publication-statusPublisheden_US
pubs.volume18en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorChoudhary, Jyotien_US


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