Pseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system

Vista sencilla de ítem
dc.contributor.authorVelasco Carneros, Lorea
dc.contributor.authorBernardo Seisdedos, Ganeko
dc.contributor.authorMaréchal, Jean-Didier
dc.contributor.authorMillet, Óscar
dc.contributor.authorMoro Pérez, Fernando
dc.contributor.authorMuga Villate, Arturo
dc.date.accessioned2025-03-11T14:30:12Z
dc.date.available2025-03-11T14:30:12Z
dc.date.issued2024-08
dc.date.updated2025-03-11T14:30:12Z
dc.description.abstractThe Hsp70 system is essential for maintaining protein homeostasis and comprises a central Hsp70 and two accessory proteins that belong to the J-domain protein (JDP) and nucleotide exchange factor families. Posttranslational modifications offer a means to tune the activity of the system. We explore how phosphorylation of specific residues of the J-domain of DNAJA2, a class A JDP, regulates Hsc70 activity using biochemical and structural approaches. Among these residues, we find that pseudophosphorylation of Y10 and S51 enhances the holding/folding balance of the Hsp70 system, reducing cochaperone collaboration with Hsc70 while maintaining the holding capacity. Truly phosphorylated J domains corroborate phosphomimetic variant effects. Notably, distinct mechanisms underlie functional impacts of these DNAJA2 variants. Pseudophosphorylation of Y10 induces partial disordering of the J domain, whereas the S51E substitution weakens essential DNAJA2-Hsc70 interactions without a large structural reorganization of the protein. S51 phosphorylation might be class-specific, as all cytosolic class A human JDPs harbor a phosphorylatable residue at this position.en
dc.description.sponsorshipBasque Government, Grant/Award Number: IT1745-22; MICIU/AEI/10.13039/501100011033, Grant/Award Number: PID2019-111068GB-I00; Viceconsejeria de Universidades e Investigación.en
dc.identifier.citationVelasco-Carneros, L., Bernardo-Seisdedos, G., Maréchal, J.-D., Millet, O., Moro, F., & Muga, A. (2024). Pseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system. Protein Science, 33(8). https://doi.org/10.1002/PRO.5105
dc.identifier.doi10.1002/PRO.5105
dc.identifier.eissn1469-896X
dc.identifier.issn0961-8368
dc.identifier.urihttps://hdl.handle.net/20.500.14454/2507
dc.language.isoeng
dc.publisherJohn Wiley and Sons Inc
dc.rights© 2024 The Author(s)
dc.subject.otherChaperone
dc.subject.otherDNAJA2
dc.subject.otherHsc70
dc.subject.otherJ-domain
dc.subject.otherPhosphorylation
dc.subject.otherProtein folding
dc.titlePseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 systemen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.issue8
oaire.citation.titleProtein Science
oaire.citation.volume33
oaire.licenseConditionhttps://creativecommons.org/licenses/by-nc-nd/4.0/
oaire.versionVoR
Archivos
Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
velasco_pseudophosphorylation_2024.pdf
Tamaño:
12.1 MB
Formato:
Adobe Portable Document Format
Descargar
Colecciones
Artículos