Molecular mechanism of J-domain-triggered ATP hydrolysis by Hsp70 chaperones

• Verfasst von: Kityk, Roman [VerfasserIn]
• Verfasst von: Kopp, Jürgen [VerfasserIn]
• Verfasst von: Mayer, Matthias P. [VerfasserIn]
• Titel: Molecular mechanism of J-domain-triggered ATP hydrolysis by Hsp70 chaperones
• Verf.angabe: Roman Kityk, Jürgen Kopp, Matthias P. Mayer
• E-Jahr: 2018
• Jahr: 18 January 2018
• Jahr des Originals: 2017
• Umfang: 15 S.
• Fussnoten: Gesehen am 15.10.2018 ; Available online 28 December 2017
• Titel Quelle: Enthalten in: Molecular cell
• Ort Quelle: [Cambridge, Mass.] : Cell Press, 1997
• Jahr Quelle: 2018
• Band/Heft Quelle: 69(2018), 2, Seite 227-237,e1-e4
• ISSN Quelle: 1097-4164
• DOI: doi:10.1016/j.molcel.2017.12.003
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: allostery
• Sach-SW: Hsp40
• Sach-SW: Hsp70
• Sach-SW: interdomain communication
• Sach-SW: molecular chaperones
• Sach-SW: protein folding
• K10plus-PPN: 1581919964

Abstract

Efficient targeting of Hsp70 chaperones to substrate proteins depends on J-domain cochaperones, which in synergism with substrates trigger ATP hydrolysis in Hsp70s and concomitant substrate trapping. We present the crystal structure of the J-domain of Escherichia coli DnaJ in complex with the E. coli Hsp70 DnaK. The J-domain interacts not only with DnaK's nucleotide-binding domain (NBD) but also with its substrate-binding domain (SBD) and packs against the highly conserved interdomain linker. Mutational replacement of contacts between J-domain and SBD strongly reduces the ability of substrates to stimulate ATP hydrolysis in the presence of DnaJ and compromises viability at heat shock temperatures. Our data demonstrate that the J-domain and the substrate do not deliver completely independent signals for ATP hydrolysis, but the J-domain, in addition to its direct influence on Hsp70s catalytic center, makes Hsp70 more responsive for the hydrolysis-inducing signal of the substrate, resulting in efficient substrate trapping.