| Structural highlights
Function
[JAC1_YEAST] Co-chaperone required for the assembly of iron-sulfur (Fe/S) clusters in mitochondria. Stimulates the ATPase activity of its specialized Hsp70 chaperone partner SSQ1. Binds to the substrate protein ISU1 and targets it to SSQ1. May function together with SSQ1 in the dislocation of the Fe/S cluster from ISU1 and its insertion into apoproteins.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The ubiquitous mitochondrial J-protein Jac1, called HscB in Escherichia coli, and its partner Hsp70 play a critical role in the transfer of Fe-S clusters from the scaffold protein Isu to recipient proteins. Biochemical results from eukaryotic and prokaryotic systems indicate that formation of the Jac1-Isu complex is important for both targeting of the Isu for Hsp70 binding and stimulation of Hsp70's ATPase activity. However, in apparent contradiction, we previously reported that an 8-fold decrease in Jac1's affinity for Isu1 is well tolerated in vivo, raising the question as to whether the Jac1:Isu interaction actually plays an important biological role. Here, we report the determination of the structure of Jac1 from Saccharomyces cerevisiae. Taking advantage of this information and recently published data from the homologous bacterial system, we determined that a total of eight surface-exposed residues play a role in Isu binding, as assessed by a set of biochemical assays. A variant having alanines substituted for these eight residues was unable to support growth of a jac1-Delta strain. However, replacement of three residues caused partial loss of function, resulting in a significant decrease in the Jac1:Isu1 interaction, a slow growth phenotype, and a reduction in the activity of Fe-S cluster-containing enzymes. Thus, we conclude that the Jac1:Isu1 interaction plays an indispensable role in the essential process of mitochondrial Fe-S cluster biogenesis.
Interaction of j-protein co-chaperone jac1 with fe-s scaffold isu is indispensable in vivo and conserved in evolution.,Ciesielski SJ, Schilke BA, Osipiuk J, Bigelow L, Mulligan R, Majewska J, Joachimiak A, Marszalek J, Craig EA, Dutkiewicz R J Mol Biol. 2012 Mar 16;417(1-2):1-12. Epub 2012 Jan 27. PMID:22306468[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Voisine C, Cheng YC, Ohlson M, Schilke B, Hoff K, Beinert H, Marszalek J, Craig EA. Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe/S clusters in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1483-8. PMID:11171977 doi:10.1073/pnas.98.4.1483
- ↑ Strain J, Lorenz CR, Bode J, Garland S, Smolen GA, Ta DT, Vickery LE, Culotta VC. Suppressors of superoxide dismutase (SOD1) deficiency in Saccharomyces cerevisiae. Identification of proteins predicted to mediate iron-sulfur cluster assembly. J Biol Chem. 1998 Nov 20;273(47):31138-44. PMID:9813017
- ↑ Kim R, Saxena S, Gordon DM, Pain D, Dancis A. J-domain protein, Jac1p, of yeast mitochondria required for iron homeostasis and activity of Fe-S cluster proteins. J Biol Chem. 2001 May 18;276(20):17524-32. Epub 2001 Feb 27. PMID:11278728 doi:10.1074/jbc.M010695200
- ↑ Lutz T, Westermann B, Neupert W, Herrmann JM. The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria. J Mol Biol. 2001 Mar 30;307(3):815-25. PMID:11273703 doi:10.1006/jmbi.2001.4527
- ↑ Muhlenhoff U, Gerber J, Richhardt N, Lill R. Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. EMBO J. 2003 Sep 15;22(18):4815-25. PMID:12970193 doi:http://dx.doi.org/10.1093/emboj/cdg446
- ↑ Dutkiewicz R, Schilke B, Knieszner H, Walter W, Craig EA, Marszalek J. Ssq1, a mitochondrial Hsp70 involved in iron-sulfur (Fe/S) center biogenesis. Similarities to and differences from its bacterial counterpart. J Biol Chem. 2003 Aug 8;278(32):29719-27. Epub 2003 May 19. PMID:12756240 doi:10.1074/jbc.M303527200
- ↑ Dutkiewicz R, Schilke B, Cheng S, Knieszner H, Craig EA, Marszalek J. Sequence-specific interaction between mitochondrial Fe-S scaffold protein Isu and Hsp70 Ssq1 is essential for their in vivo function. J Biol Chem. 2004 Jul 9;279(28):29167-74. Epub 2004 Apr 30. PMID:15123690 doi:10.1074/jbc.M402947200
- ↑ Dutkiewicz R, Marszalek J, Schilke B, Craig EA, Lill R, Muhlenhoff U. The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p. J Biol Chem. 2006 Mar 24;281(12):7801-8. Epub 2006 Jan 23. PMID:16431909 doi:M513301200
- ↑ Andrew AJ, Dutkiewicz R, Knieszner H, Craig EA, Marszalek J. Characterization of the interaction between the J-protein Jac1p and the scaffold for Fe-S cluster biogenesis, Isu1p. J Biol Chem. 2006 May 26;281(21):14580-7. Epub 2006 Mar 21. PMID:16551614 doi:10.1074/jbc.M600842200
- ↑ Ciesielski SJ, Schilke BA, Osipiuk J, Bigelow L, Mulligan R, Majewska J, Joachimiak A, Marszalek J, Craig EA, Dutkiewicz R. Interaction of j-protein co-chaperone jac1 with fe-s scaffold isu is indispensable in vivo and conserved in evolution. J Mol Biol. 2012 Mar 16;417(1-2):1-12. Epub 2012 Jan 27. PMID:22306468 doi:10.1016/j.jmb.2012.01.022
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