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dc.contributor.authorPatel, Pryank
dc.contributor.authorPrescott, Gerald R.
dc.contributor.authorBurgoyne, Robert D
dc.contributor.authorLian, Lu-Yun
dc.contributor.authorMorgan, Alan
dc.date.accessioned2016-11-11T15:59:58Z
dc.date.available2016-11-11T15:59:58Z
dc.date.issued2016-07-21
dc.identifier.citationPatel , P , Prescott , G R , Burgoyne , R D , Lian , L-Y & Morgan , A 2016 , ' Phosphorylation of Cysteine String Protein Triggers a Major Conformational Switch ' , Structure , vol. 24 , no. 8 , pp. 1380-1386 . https://doi.org/10.1016/j.str.2016.06.009
dc.identifier.issn0969-2126
dc.identifier.otherPURE: 10317009
dc.identifier.otherPURE UUID: f985949a-6f38-4aa6-a32b-8dc15e8b95b6
dc.identifier.otherScopus: 84979987518
dc.identifier.urihttp://hdl.handle.net/2299/17315
dc.descriptionThis is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.description.abstractCysteine string protein (CSP) is a member of the DnaJ/Hsp40 chaperone family that localizes to neuronal synaptic vesicles. Impaired CSP function leads to neurodegeneration in humans and model organisms as a result of misfolding of client proteins involved in neurotransmission. Mammalian CSP is phosphorylated in vivo on Ser10, and this modulates its protein interactions and effects on neurotransmitter release. However, there are no data on the structural consequences of CSP phosphorylation to explain these functional effects. We show that Ser10 phosphorylation causes an order-to-disorder transition that disrupts CSP's extreme N-terminal α helix. This triggers the concomitant formation of a hairpin loop stabilized by ionic interactions between phosphoSer10 and the highly conserved J-domain residue, Lys58. These phosphorylation-induced effects result in significant changes to CSP conformation and surface charge distribution. The phospho-switch revealed here provides structural insight into how Ser10 phosphorylation modulates CSP function and also has potential implications for other DnaJ phosphoproteins.en
dc.format.extent7
dc.language.isoeng
dc.relation.ispartofStructure
dc.rightsOpen
dc.subjectadult onset neuronal lipofuscinosis
dc.subjectchaperone
dc.subjectDnaJ
dc.subjectHsp40
dc.subjectneurodegeneration
dc.titlePhosphorylation of Cysteine String Protein Triggers a Major Conformational Switchen
dc.contributor.institutionBiochemistry and Bioinformatics
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionBiosciences Research Group
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2016-07-21
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.str.2016.06.009
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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