Molecular Mechanism of J-Domain-Triggered ATP Hydrolysis by Hsp70 Chaperones
Molecular Mechanism of J-Domain-Triggered ATP Hydrolysis by Hsp70 Chaperones
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DOI：
10.1016/j.molcel.2017.12.003
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发表时间：
2018-01-18
期刊：
影响因子：
16
通讯作者：
Mayer, Matthias P.
中科院分区：
文献类型：
--
作者：
Kityk, Roman;Kopp, Juergen;Mayer, Matthias P.
Hsp70分子伴侣对底物蛋白质的有效靶向依赖于J-结构域的辅分子伴侣蛋白，它与底物协同作用，在Hsp70中触发ATP水解酶，并伴随底物捕获。我们报道了大肠杆菌DNAJ与大肠杆菌Hsp70 DNAK的复合体的晶体结构。J-结构域不仅与DNAK的核苷酸结合域(NBD)相互作用，而且与其底物结合域(SBD)相互作用，并与高度保守的域间连接子相互作用。J结构域和SBD之间接触的突变替换大大降低了底物在DNAJ存在下刺激ATP水解的能力，并损害了在热休克温度下的生存能力。我们的数据表明，J-结构域和底物并不是完全独立地传递ATP水解信号，但J-结构域除了直接影响Hsp70催化中心外，还使Hsp70对底物的水解诱导信号更敏感，从而有效地捕获底物。
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.