title: Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches.
abstract: 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.
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, 80-308, Poland.|Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, 14853-1301.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Mozolewska
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, 80-308, Poland.|Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, 14853-1301.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krupa
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, 14853-1301.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, 80-308, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Liwo
mesh_terms: D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C121520:ISU1 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; C115914:JAC1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins
keywords: Isu1-Jac1 interactions; J-protein; UNited RESidue (UNRES) force field; homology modeling; iron-sulfur cluster biogenesis; iron-sulfur protein 1