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dc.contributor.authorMyrum, Craigen_US
dc.contributor.authorBaumann, Anneen_US
dc.contributor.authorBustad, Helene J.en_US
dc.contributor.authorFlydal, Marte Innselseten_US
dc.contributor.authorMariaule, Vincenten_US
dc.contributor.authorAlvira, Saraen_US
dc.contributor.authorCuéllar, Jorgeen_US
dc.contributor.authorHaavik, Janen_US
dc.contributor.authorSoulé, Jonathanen_US
dc.contributor.authorValpuesta, José Maríaen_US
dc.contributor.authorMárquez, José Antonioen_US
dc.contributor.authorMartinez, Auroraen_US
dc.contributor.authorBramham, Clive R.en_US
dc.PublishedBiochemical Journal 2015, 468(1):145-158eng
dc.description.abstractThe immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskeletal structures or other polyanionic surfaces, whereas the C-terminal domain is acidic and stabilized by ionic conditions that promote oligomerization. Upon binding of presenilin-1 (PS1) peptide, hArc undergoes a large structural change. A non-synonymous genetic variant of hArc (V231G) showed properties similar to the wild-type (WT) protein. We conclude that hArc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes.en_US
dc.publisherPortland Presseng
dc.rightsAttribution CC BYeng
dc.subjectbiophysical characterizationeng
dc.subjectprotein purificationeng
dc.subjectprotein stabilityeng
dc.subjectsynaptic plasticityeng
dc.titleArc is a flexible modular protein capable of reversible self-oligomerizationen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2015 The Authors
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk biokjemi: 726
dc.subject.nsiVDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical biochemistry: 726

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