Structural highlights
Function
[DNAK_ECOLI] Plays an essential role in the initiation of phage lambda DNA replication, where it acts in an ATP-dependent fashion with the DnaJ protein to release lambda O and P proteins from the preprimosomal complex. DnaK is also involved in chromosomal DNA replication, possibly through an analogous interaction with the DnaA protein. Also participates actively in the response to hyperosmotic shock.[HAMAP-Rule:MF_00332] [DNAJ_ECOLI] Interacts with DnaK and GrpE to disassemble a protein complex at the origins of replication of phage lambda and several plasmids. Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins and by disaggregating proteins, also in an autonomous, DnaK-independent fashion. Unfolded proteins bind initially to DnaJ; upon interaction with the DnaJ-bound protein, DnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from DnaK; ATP binding to DnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between DnaJ, DnaK and GrpE are required for fully efficient folding.[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Molecular Mechanism of J-Domain-Triggered ATP Hydrolysis by Hsp70 Chaperones.,Kityk R, Kopp J, Mayer MP Mol Cell. 2017 Dec 27. pii: S1097-2765(17)30931-0. doi:, 10.1016/j.molcel.2017.12.003. PMID:29290615[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liberek K, Marszalek J, Ang D, Georgopoulos C, Zylicz M. Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2874-8. PMID:1826368
- ↑ Zietkiewicz S, Krzewska J, Liberek K. Successive and synergistic action of the Hsp70 and Hsp100 chaperones in protein disaggregation. J Biol Chem. 2004 Oct 22;279(43):44376-83. Epub 2004 Aug 9. PMID:15302880 doi:http://dx.doi.org/10.1074/jbc.M402405200
- ↑ Siegenthaler RK, Grimshaw JP, Christen P. Immediate response of the DnaK molecular chaperone system to heat shock. FEBS Lett. 2004 Mar 26;562(1-3):105-10. PMID:15044009 doi:http://dx.doi.org/10.1016/S0014-5793(04)00190-5
- ↑ Zzaman S, Reddy JM, Bastia D. The DnaK-DnaJ-GrpE chaperone system activates inert wild type pi initiator protein of R6K into a form active in replication initiation. J Biol Chem. 2004 Dec 3;279(49):50886-94. Epub 2004 Oct 13. PMID:15485812 doi:http://dx.doi.org/M407531200
- ↑ Kityk R, Kopp J, Mayer MP. Molecular Mechanism of J-Domain-Triggered ATP Hydrolysis by Hsp70 Chaperones. Mol Cell. 2017 Dec 27. pii: S1097-2765(17)30931-0. doi:, 10.1016/j.molcel.2017.12.003. PMID:29290615 doi:http://dx.doi.org/10.1016/j.molcel.2017.12.003
