Structural Properties of [2Fe-2S] ISCA2-IBA57: a Complex of the Mitochondrial Iron-sulfur Cluster Assembly Machinery

Overview

Journal Sci Rep

Specialty Science

Date 2019 Dec 14

PMID 31831856

Citations 13

Authors

Veronica Nasta

Stefano Da Vela

Spyridon Gourdoupis

Simone Ciofi-Baffoni

Dmitri I Svergun

Lucia Banci

Affiliations

Soon will be listed here.

Abstract

In mitochondria, a complex protein machinery is devoted to the maturation of iron-sulfur cluster proteins. Structural information on the last steps of the machinery, which involve ISCA1, ISCA2 and IBA57 proteins, needs to be acquired in order to define how these proteins cooperate each other. We report here the use of an integrative approach, utilizing information from small-angle X-ray scattering (SAXS) and bioinformatics-driven docking prediction, to determine a low-resolution structural model of the human mitochondrial [2Fe-2S] ISCA2-IBA57 complex. In the applied experimental conditions, all the data converge to a structural organization of dimer of dimers for the [2Fe-2S] ISCA2-IBA57 complex with ISCA2 providing the homodimerization core interface. The [2Fe-2S] cluster is out of the ISCA2 core while being shared with IBA57 in the dimer. The specific interaction pattern identified from the dimeric [2Fe-2S] ISCA2-IBA57 structural model allowed us to define the molecular grounds of the pathogenic Arg146Trp mutation of IBA57. This finding suggests that the dimeric [2Fe-2S] ISCA2-IBA57 hetero-complex is a physiologically relevant species playing a role in mitochondrial [4Fe-4S] protein biogenesis.

Citing Articles

Defects in the Maturation of Mitochondrial Iron-Sulfur Proteins: Biophysical Investigation of the MMDS3 Causing Gly104Cys Variant of IBA57.

Bargagna B, Staderini T, Lang S, Banci L, Camponeschi F Int J Mol Sci. 2024; 25(19).

PMID: 39408793 PMC: 11476781. DOI: 10.3390/ijms251910466.

On the evolutionary trail of MagRs.

Zhang J, Chang Y, Zhang P, Zhang Y, Wei M, Han C Zool Res. 2024; 45(4):821-830.

PMID: 38894524 PMC: 11298677. DOI: 10.24272/j.issn.2095-8137.2024.074.

Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.

Yan T, Julio A, Villanueva M, Jones A, Ball A, Boatner L Cell Chem Biol. 2023; 30(7):811-827.e7.

PMID: 37419112 PMC: 10510412. DOI: 10.1016/j.chembiol.2023.06.008.

Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway.

Da Vela S, Saudino G, Lucarelli F, Banci L, Svergun D, Ciofi-Baffoni S J Mol Biol. 2023; 435(15):168154.

PMID: 37211204 PMC: 10388178. DOI: 10.1016/j.jmb.2023.168154.

Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.

Yan T, Julio A, Villanueva M, Jones A, Ball A, Boatner L bioRxiv. 2023; .

PMID: 36711448 PMC: 9882296. DOI: 10.1101/2023.01.22.525042.

References

Toldo I, Nosadini M, Boscardin C, Talenti G, Manara R, Lamantea E . Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations. Metab Brain Dis. 2018; 33(3):805-812. DOI: 10.1007/s11011-017-0181-3. View

Ye H, Jeong S, Ghosh M, Kovtunovych G, Silvestri L, Ortillo D . Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J Clin Invest. 2010; 120(5):1749-61. PMC: 2860907. DOI: 10.1172/JCI40372. View

Ishiyama A, Sakai C, Matsushima Y, Noguchi S, Mitsuhashi S, Endo Y . mutations abrogate iron-sulfur cluster assembly leading to cavitating leukoencephalopathy. Neurol Genet. 2017; 3(5):e184. PMC: 5591399. DOI: 10.1212/NXG.0000000000000184. View

Koradi R, Billeter M, Wuthrich K . MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph. 1996; 14(1):51-5, 29-32. DOI: 10.1016/0263-7855(96)00009-4. View

van Zundert G, Rodrigues J, Trellet M, Schmitz C, Kastritis P, Karaca E . The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes. J Mol Biol. 2015; 428(4):720-725. DOI: 10.1016/j.jmb.2015.09.014. View

Maio N, Rouault T . Iron-sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery. Biochim Biophys Acta. 2014; 1853(6):1493-512. PMC: 4366362. DOI: 10.1016/j.bbamcr.2014.09.009. View

Petoukhov M, Svergun D . Global rigid body modeling of macromolecular complexes against small-angle scattering data. Biophys J. 2005; 89(2):1237-50. PMC: 1366608. DOI: 10.1529/biophysj.105.064154. View

Panjkovich A, Svergun D . CHROMIXS: automatic and interactive analysis of chromatography-coupled small-angle X-ray scattering data. Bioinformatics. 2018; 34(11):1944-1946. PMC: 5972624. DOI: 10.1093/bioinformatics/btx846. View

Lossos A, Stumpfig C, Stevanin G, Gaussen M, Zimmerman B, Mundwiller E . Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015; 84(7):659-67. DOI: 10.1212/WNL.0000000000001270. View

10.

Bilder P, Ding H, Newcomer M . Crystal structure of the ancient, Fe-S scaffold IscA reveals a novel protein fold. Biochemistry. 2004; 43(1):133-9. DOI: 10.1021/bi035440s. View

11.

Waller J, Alvarez S, Naponelli V, Lara-Nunez A, Blaby I, da Silva V . A role for tetrahydrofolates in the metabolism of iron-sulfur clusters in all domains of life. Proc Natl Acad Sci U S A. 2010; 107(23):10412-7. PMC: 2890791. DOI: 10.1073/pnas.0911586107. View

12.

Uzarska M, Dutkiewicz R, Freibert S, Lill R, Muhlenhoff U . The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation. Mol Biol Cell. 2013; 24(12):1830-41. PMC: 3681689. DOI: 10.1091/mbc.E12-09-0644. View

13.

Wada K, Hasegawa Y, Gong Z, Minami Y, Fukuyama K, Takahashi Y . Crystal structure of Escherichia coli SufA involved in biosynthesis of iron-sulfur clusters: implications for a functional dimer. FEBS Lett. 2005; 579(29):6543-8. DOI: 10.1016/j.febslet.2005.10.046. View

14.

Blanchet C, Spilotros A, Schwemmer F, Graewert M, Kikhney A, Jeffries C . Versatile sample environments and automation for biological solution X-ray scattering experiments at the P12 beamline (PETRA III, DESY). J Appl Crystallogr. 2015; 48(Pt 2):431-443. PMC: 4379436. DOI: 10.1107/S160057671500254X. View

15.

Morimoto K, Yamashita E, Kondou Y, Lee S, Arisaka F, Tsukihara T . The asymmetric IscA homodimer with an exposed [2Fe-2S] cluster suggests the structural basis of the Fe-S cluster biosynthetic scaffold. J Mol Biol. 2006; 360(1):117-32. DOI: 10.1016/j.jmb.2006.04.067. View

16.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View

17.

de Vries S, van Dijk A, Bonvin A . WHISCY: what information does surface conservation yield? Application to data-driven docking. Proteins. 2006; 63(3):479-89. DOI: 10.1002/prot.20842. View

18.

Franke D, Petoukhov M, Konarev P, Panjkovich A, Tuukkanen A, Mertens H . : a comprehensive data analysis suite for small-angle scattering from macromolecular solutions. J Appl Crystallogr. 2017; 50(Pt 4):1212-1225. PMC: 5541357. DOI: 10.1107/S1600576717007786. View

19.

Sali A, Blundell T . Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993; 234(3):779-815. DOI: 10.1006/jmbi.1993.1626. View

20.

Cupp-Vickery J, Silberg J, Ta D, Vickery L . Crystal structure of IscA, an iron-sulfur cluster assembly protein from Escherichia coli. J Mol Biol. 2004; 338(1):127-37. DOI: 10.1016/j.jmb.2004.02.027. View