Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability

Saha, Prasenjit Prasad; Srivastava, Shubhi; Kumar, S. K. Praveen; Sinha, Devanjan; D’Silva, Patrick

doi:10.1074/jbc.m115.678508

Cited by 23 publications

(14 citation statements)

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“…As mentioned previously, it was found that NFS1 and ISD11 interact in human mitochondria, suggesting that the last would be required for the assembly of Fe-S proteins [ 38 ]. Moreover, the critical amino acid residues for the interaction have been mapped [ 47 ]. Recently, it was reported the structure of a heterodecamer multiprotein complex that would be key for the biosynthesis of mitochondrial Fe-S clusters in humans containing two copies of each of NFS1, frataxin (FXN), ISCU, ISD11, and ACP [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

“…A secondary structure prediction shows that AtISD11 has 2 helix domains close to the N-terminus of the protein and they are well conserved ( Figure 4 A). It was described that Arg68 from human ISD11 is critical for the interaction with NFS1, but also other amino acid residues are involved in ISD11 stabilization of NFS1 such as Phe40 and Leu63 [ 47 ]. We found that Phe40, Leu63, and Arg68 are conserved in AtISD11 (Phe38, Leu61, and Arg66, AtISD11 numbering) ( Figure 4 B).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…It was previously described that human NFS1 interacts with ISD11 and this interaction stabilizes NFS1, preventing its aggregation [ 38 , 45 , 47 ]. The amino acid residues involved in such interaction were mapped and results showed that some residues present in the helix regions of the ISD11 protein would have an essential role in the interaction [ 47 ]. Moreover, it has recently been shown in human mitochondria that the complex involved in the synthesis of Fe-S clusters is a heterodecamer composed of five proteins: NFS1, frataxin, the scaffold protein ISCU, ISD11, and an acyl-carrier protein (ACP) [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

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Iron-Sulfur Cluster Complex Assembly in the Mitochondria of Arabidopsis thaliana

Armas

Balparda

Terenzi

et al. 2020

Plants

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In plants, the cysteine desulfurase (AtNFS1) and frataxin (AtFH) are involved in the formation of Fe-S groups in mitochondria, specifically, in Fe and sulfur loading onto scaffold proteins, and the subsequent formation of the mature Fe-S cluster. We found that the small mitochondrial chaperone, AtISD11, and AtFH are positive regulators for AtNFS1 activity in Arabidopsis. Moreover, when the three proteins were incubated together, a stronger attenuation of the Fenton reaction was observed compared to that observed with AtFH alone. Using pull-down assays, we found that these three proteins physically interact, and sequence alignment and docking studies showed that several amino acid residues reported as critical for the interaction of their human homologous are conserved. Our results suggest that AtFH, AtNFS1 and AtISD11 form a multiprotein complex that could be involved in different stages of the iron–sulfur cluster (ISC) pathway in plant mitochondria.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Iron-Sulfur Cluster Complex Assembly in the Mitochondria of Arabidopsis thaliana

Armas

Balparda

Terenzi

et al. 2020

Plants

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“…In contrast to Escherichia coli ( E. coli ) cysteine desulfurase IscS, NFS1 requires the adaptor protein ISD11 in order to maintain its activity. The NFS1-ISD11 complex is essential for nuclear and mitochondrial iron-sulfur protein biosynthesis, moreover, the homozygous R68L ISD11 mutation causes the mitochondrial genetic disorder COXPD19 [ 6 , 7 ]. However, the homology of the eukaryotic ISD11 protein has not been identified in the prokaryote to date.…”

Section: Introductionmentioning

confidence: 99%

Expression of soluble native protein in Escherichia coli using a cold-shock SUMO tag-fused expression vector

Li¹,

Han²,

Zhang³

et al. 2018

Biotechnology Reports

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Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria

et al. 2019

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In the era of genomics, the number of genes linked to mitochondrial disease has been quickly growing, producing massive knowledge on mitochondrial biochemistry. LYRM4 gene codifies for ISD11, a small protein (11 kDa) acting as an iron‐sulfur cluster, that has been recently confirmed as a disease‐causing gene for mitochondrial disorders. We present a 4‐year‐old girl patient, born from non‐consanguineous healthy parents, with two episodes of cardiorespiratory arrest after respiratory viral illness with progressive decreased activity and lethargy, at the age of 2 and 3 years. She was asymptomatic between crisis with regular growth and normal development. During acute events of illness, she had hyperlactacidemia (maximum lactate 5.2 mmol/L) and urinary excretion of ketone bodies and 3‐methylglutaconic acid, which are normalized after recovery. A Next Generation Sequence approach with a broad gene panel designed for mitochondrial disorders revealed a novel probably pathogenic variant in homozygosity in the LYRM4 gene [p.Tyr31Cys (c.92A>G)] with Mendelian segregation. Functional studies in the skeletal muscle confirmed a combined deficiency of the mitochondrial respiratory chain (I, II, and IV complexes). To our knowledge, this is the third case of LYRM4 deficiency worldwide and the first with 3‐methylglutaconic aciduria, not reported in any Fe‐S cluster deficiency. Remarkably, it appears to be no neurological involvement so far, only with life‐threating acute crisis triggered by expectably benign autolimited illnesses. Respiratory chain cofactors and chaperones are a new field of knowledge and can play a remarkable effect in system homeostasis.

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Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability

Cited by 23 publications

References 50 publications

Iron-Sulfur Cluster Complex Assembly in the Mitochondria of Arabidopsis thaliana

Iron-Sulfur Cluster Complex Assembly in the Mitochondria of Arabidopsis thaliana

Expression of soluble native protein in Escherichia coli using a cold-shock SUMO tag-fused expression vector

Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria

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