The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
Velasco-Carneros, Lorea (Universidad del País Vasco)
Cuéllar, Jorge (CNB-CSIC)
Dublang, Leire (Universidad del País Vasco)
Santiago, César (CNB-CSIC)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)
Martín-Benito, Jaime (CNB-CSIC)
Maestro, Moisés (CNB-CSIC)
Fernández-Higuero, José Ángel (Universidad del País Vasco)
Orozco, Natalia (Universidad del País Vasco)
Moro, Fernando (Universidad del País Vasco)
Valpuesta, Jose María (CNB-CSIC)
Muga, Arturo (Universidad del País Vasco)

Fecha:	2023
Resumen:	J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70. J-domain proteins (JDPs) regulate Hsp70 function and specificity. Here, authors combine functional assays and cryoEM to describe the structure of a dynamic tubular assembly of DNAJA2, a class A JDP, and its stabilizing interdomain interactions.
Ayudas:	Agencia Estatal de Investigación PID2019-111068GB-I00 Agencia Estatal de Investigación PID2020-117752RB-I00 Agencia Estatal de Investigación PID2019-105872GB-I00 Agencia Estatal de Investigación PID2022-137175NB-I00
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cryoelectron microscopy ; Chaperones
Publicado en:	Nature communications, Vol. 14 (September 2023) , art. 5436, ISSN 2041-1723
Obra relacionada:	Velasco-Carneros, Lorea; Cuéllar, Jorge; Dublang, Leire; [et al.]. «Author Correction : The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70». Nature communications, Vol. 15 (January 2024), art. 99 https://doi.org/10.1038/s41467-023-44499-y

Correcció de l'article: https://ddd.uab.cat/record/311183
DOI: 10.1038/s41467-023-41150-8
PMID: 37670029

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