Mozolewska Magdalena A, Krupa Paweł, Scheraga Harold A, Liwo Adam
Faculty of Chemistry, University of Gdansk, Gdansk, 80-308, Poland.
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, 14853-1301.
Proteins. 2015 Aug;83(8):1414-26. doi: 10.1002/prot.24824. Epub 2015 Jun 6.
The iron-sulfur protein 1 (Isu1) and the J-type co-chaperone Jac1 from yeast are part of a huge ATP-dependent system, and both interact with Hsp70 chaperones. Interaction of Isu1 and Jac1 is a part of the iron-sulfur cluster biogenesis system in mitochondria. In this study, the structure and dynamics of the yeast Isu1-Jac1 complex has been modeled. First, the complete structure of Isu1 was obtained by homology modeling using the I-TASSER server and YASARA software and thereafter tested for stability in the all-atom force field AMBER. Then, the known experimental structure of Jac1 was adopted to obtain initial models of the Isu1-Jac1 complex by using the ZDOCK server for global and local docking and the AutoDock software for local docking. Three most probable models were subsequently subjected to the coarse-grained molecular dynamics simulations with the UNRES force field to obtain the final structures of the complex. In the most probable model, Isu1 binds to the left face of the Γ-shaped Jac1 molecule by the β-sheet section of Isu1. Residues L105 , L109 , and Y163 of Jac1 have been assessed by mutation studies to be essential for binding (Ciesielski et al., J Mol Biol 2012; 417:1-12). These residues were also found, by UNRES/molecular dynamics simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N(95), T(98), P(102), H(112), V(159), L(167), and A(170) of Jac1, not yet tested experimentally, were also found to be important in binding.
酵母中的铁硫蛋白1（Isu1）和J型共伴侣蛋白Jac1是一个庞大的ATP依赖性系统的组成部分，二者均与Hsp70伴侣蛋白相互作用。Isu1与Jac1的相互作用是线粒体中铁硫簇生物合成系统的一部分。在本研究中，对酵母Isu1-Jac1复合物的结构和动力学进行了建模。首先，使用I-TASSER服务器和YASARA软件通过同源建模获得Isu1的完整结构，然后在全原子力场AMBER中测试其稳定性。接着，采用已知的Jac1实验结构，使用ZDOCK服务器进行全局和局部对接以及AutoDock软件进行局部对接，以获得Isu1-Jac1复合物的初始模型。随后，对三个最可能的模型使用UNRES力场进行粗粒度分子动力学模拟，以获得复合物的最终结构。在最可能的模型中，Isu1通过其β折叠部分与Γ形Jac1分子的左侧面结合。通过突变研究评估发现，Jac1的L105、L109和Y163残基对于结合至关重要（Ciesielski等人，《分子生物学杂志》2012年；417:1-12）。通过UNRES/分子动力学模拟还发现，这些残基参与了复合物中Isu1与Jac1之间的强相互作用。此外，尚未经过实验测试的Jac1的N(95)、T(98)、P(102)、H(112)、V(159)、L(167)和A(170)残基在结合中也很重要。
