7ZHS

3D reconstruction of the cylindrical assembly of DnaJA2 delta G/F by imposing D5 symmetry

Summary for 7ZHS

• Entry DOI: 10.2210/pdb7zhs/pdb
• EMDB information: 14736
• Descriptor: Ubiquitin-like protein SMT3,DnaJ homolog subfamily A member 2, ZINC ION (2 entities in total)
• Functional Keywords: oligomer, filaments, helix, holdase, foldase, hsp40, dnaja2, hsp70 co-chaperone, chaperone
• Biological source: Saccharomyces cerevisiae S288c; More
• Total number of polymer chains: 40
• Total formula weight: 2244471.16

Authors

Cuellar, J.,Velasco-Carneros, L.,Santiago, C.,Martin-Benito, J.,Valpuesta, J.,Muga, A. (deposition date: 2022-04-07, release date: 2023-07-26, Last modification date: 2024-01-24)

Primary citation

Velasco-Carneros, L.,Cuellar, J.,Dublang, L.,Santiago, C.,Marechal, J.D.,Martin-Benito, J.,Maestro, M.,Fernandez-Higuero, J.A.,Orozco, N.,Moro, F.,Valpuesta, J.M.,Muga, A.
The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70.
Nat Commun, 14:5436-5436, 2023

PubMed Abstract: 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.

PubMed: 37670029
DOI: 10.1038/s41467-023-41150-8

Experimental method

ELECTRON MICROSCOPY (6.9 Å)