title: The Eukaryotic-Specific ISD11 Is a Complex-Orphan Protein with Ability to Bind the Prokaryotic IscS.
abstract: The eukaryotic protein Isd11 is a chaperone that binds and stabilizes the central component of the essential metabolic pathway responsible for formation of iron-sulfur clusters in mitochondria, the desulfurase Nfs1. Little is known about the exact role of Isd11. Here, we show that human Isd11 (ISD11) is a helical protein which exists in solution as an equilibrium between monomer, dimeric and tetrameric species when in the absence of human Nfs1 (NFS1). We also show that, surprisingly, recombinant ISD11 expressed in E. coli co-purifies with the bacterial orthologue of NFS1, IscS. Binding is weak but specific suggesting that, despite the absence of Isd11 sequences in bacteria, there is enough conservation between the two desulfurases to retain a similar mode of interaction. This knowledge may inform us on the conservation of the mode of binding of Isd11 to the desulfurase. We used evolutionary evidence to suggest Isd11 residues involved in the interaction.
authors.affiliation: Maurice Wohl Institute, King's College London, 5 Cutcombe Rd, SE5, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Friemel
authors.affiliation: Maurice Wohl Institute, King's College London, 5 Cutcombe Rd, SE5, London, United Kingdom.
authors.forename: Claudia
authors.initials: C
authors.lastname: Aloisi
authors.affiliation: CMBI 260, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Huynen
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, United Kingdom.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Taylor
authors.affiliation: Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Leimkühler
authors.affiliation: Maurice Wohl Institute, King's College London, 5 Cutcombe Rd, SE5, London, United Kingdom.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000595:Amino Acid Sequence; D013437:Carbon-Sulfur Lyases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D035925:Iron-Regulatory Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D035925:Iron-Regulatory Proteins; C544445:LYRM4 protein, human; D011994:Recombinant Proteins; D013437:Carbon-Sulfur Lyases; C513492:NFS1 protein, human; C080546:cysteine desulfurase