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dc.contributor.authorChapple, JPen_US
dc.contributor.authorHardcastle, AJen_US
dc.contributor.authorGrayson, Cen_US
dc.contributor.authorWillison, KRen_US
dc.contributor.authorCheetham, MEen_US
dc.date.accessioned2018-09-17T15:18:45Z
dc.date.issued2002-06en_US
dc.identifier6en_US
dc.identifier.citationINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2002, 43 pp. 2015 - 2020en_US
dc.identifier.issn0146-0404en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2754
dc.description.abstractPURPOSE. The X-linked retinitis pigmentosa protein RP2 is predominantly targeted to the plasma membrane. This study delineates the exact amino acid sequence requirements for targeting of RP2 through dual N-terminal acyl modification. METHODS. Inhibition of acyl modification with a palmitate analogue was used to confirm the mechanism of intracellular targeting. Mutagenesis of the first 15 residues in a synthetic RP2-green fluorescent protein (GFP) chimera was used to probe the precise requirements for plasma membrane targeting in Chinese hamster ovary (CHO) cells by confocal microscopy and subcellular fractionation. RESULTS. The N-terminal Met-Gly-Cys-X-Phe-Ser-Lys motif of human RP2 is necessary and sufficient for the protein’s plasma membrane localization. This motif includes the accepted consensus sequence for N-myristoyl transferase (NMT) and a site for attachment of a palmitoyl moiety. An interesting feature of the motif is an essential phenylalanine at position 5. This is the first report of the requirement of a specific residue at position 5 within the N-terminal acyl modification motif for normal intracellular targeting. Arginine at position 8 is not essential for plasma membrane localization of the protein, but it improves targeting. The motif is highly conserved and is found in all vertebrate orthologues of human RP2, except mouse. In mouse, however, the Ser6Thr change is concordant with the accepted NMT consensus sequence. CONCLUSIONS. Conserved residues mediate the intracellular targeting of RP2, further highlighting the potential significance of the protein’s plasma membrane localization. The delineation of this motif identifies residues in which mutations disrupt the dual acylation of RP2 and almost certainly result in disease.en_US
dc.format.extent2015 - 2020en_US
dc.titleDelineation of the plasma membrane targeting domain of the X-linked retinitis pigmentosa protein RP2en_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2002-06en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCEen_US
pubs.notesresearcherid-numbers: Cheetham, Michael/B-4672-2011 orcid-numbers: Cheetham, Michael/0000-0001-6429-654X unique-id: ISI:000175927800048en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Chromatin Regulation
pubs.volume43en_US
pubs.embargo.termsNot knownen_US
icr.researchteamChromatin Regulationen_US
dc.contributor.icrauthorWillison, Keithen_US


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