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Structural and functional characterization of a frataxin from a thermophilic organism

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Structural and functional characterization of a frataxin from a thermophilic organism. / Rasheed, Masooma; Jamshidiha, Mostafa; Puglisi, Rita; Yan, Robert; Cota, Ernesto; Pastore, Annalisa.

In: FEBS Journal, Vol. 286, No. 3, 01.02.2019, p. 495-506.

Research output: Contribution to journalArticle

Harvard

Rasheed, M, Jamshidiha, M, Puglisi, R, Yan, R, Cota, E & Pastore, A 2019, 'Structural and functional characterization of a frataxin from a thermophilic organism', FEBS Journal, vol. 286, no. 3, pp. 495-506. https://doi.org/10.1111/febs.14750

APA

Rasheed, M., Jamshidiha, M., Puglisi, R., Yan, R., Cota, E., & Pastore, A. (2019). Structural and functional characterization of a frataxin from a thermophilic organism. FEBS Journal, 286(3), 495-506. https://doi.org/10.1111/febs.14750

Vancouver

Rasheed M, Jamshidiha M, Puglisi R, Yan R, Cota E, Pastore A. Structural and functional characterization of a frataxin from a thermophilic organism. FEBS Journal. 2019 Feb 1;286(3):495-506. https://doi.org/10.1111/febs.14750

Author

Rasheed, Masooma ; Jamshidiha, Mostafa ; Puglisi, Rita ; Yan, Robert ; Cota, Ernesto ; Pastore, Annalisa. / Structural and functional characterization of a frataxin from a thermophilic organism. In: FEBS Journal. 2019 ; Vol. 286, No. 3. pp. 495-506.

Bibtex Download

@article{fa23f58e223342c48449fb9509ef4f59,
title = "Structural and functional characterization of a frataxin from a thermophilic organism",
abstract = "Frataxins form an interesting family of iron‐binding proteins with an almost unique fold and are highly conserved from bacteria to primates. They have a pivotal role in iron‐sulfur cluster biogenesis as regulators of the rates of cluster formation, as it is testified by the fact that frataxin absence is incompatible with life and reduced levels of the protein lead to the recessive neurodegenerative disease Friedreich's ataxia. Despite its importance, the structure of frataxin has been solved only from relatively few species. Here, we discuss the X‐ray structure of frataxin from the thermophilic fungus Chaetomium thermophilum, and the characterization of its interactions and dynamics in solution. We show that this eukaryotic frataxin has an unusual variation of the classical frataxin fold: the last helix is shorter than in other frataxins which results in a less symmetrical and compact structure. The stability of this protein is comparable to that of human frataxin, currently the most stable amongst the frataxin orthologues. We also characterized the iron‐binding mode of C. thermophilum frataxin and demonstrated that it binds it through a semi‐conserved negatively charged ridge on the first helix and beta‐strand. Moreover, this frataxin is also able to bind the bacterial ortholog of the desulfurase, which is central in iron‐sulfur cluster synthesis, and act as its inhibitor.",
keywords = "Friedreich's ataxia, iron–sulfur clusters, structural biology",
author = "Masooma Rasheed and Mostafa Jamshidiha and Rita Puglisi and Robert Yan and Ernesto Cota and Annalisa Pastore",
year = "2019",
month = feb,
day = "1",
doi = "10.1111/febs.14750",
language = "English",
volume = "286",
pages = "495--506",
journal = "FEBS Journal",
issn = "1742-464X",
number = "3",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Structural and functional characterization of a frataxin from a thermophilic organism

AU - Rasheed, Masooma

AU - Jamshidiha, Mostafa

AU - Puglisi, Rita

AU - Yan, Robert

AU - Cota, Ernesto

AU - Pastore, Annalisa

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Frataxins form an interesting family of iron‐binding proteins with an almost unique fold and are highly conserved from bacteria to primates. They have a pivotal role in iron‐sulfur cluster biogenesis as regulators of the rates of cluster formation, as it is testified by the fact that frataxin absence is incompatible with life and reduced levels of the protein lead to the recessive neurodegenerative disease Friedreich's ataxia. Despite its importance, the structure of frataxin has been solved only from relatively few species. Here, we discuss the X‐ray structure of frataxin from the thermophilic fungus Chaetomium thermophilum, and the characterization of its interactions and dynamics in solution. We show that this eukaryotic frataxin has an unusual variation of the classical frataxin fold: the last helix is shorter than in other frataxins which results in a less symmetrical and compact structure. The stability of this protein is comparable to that of human frataxin, currently the most stable amongst the frataxin orthologues. We also characterized the iron‐binding mode of C. thermophilum frataxin and demonstrated that it binds it through a semi‐conserved negatively charged ridge on the first helix and beta‐strand. Moreover, this frataxin is also able to bind the bacterial ortholog of the desulfurase, which is central in iron‐sulfur cluster synthesis, and act as its inhibitor.

AB - Frataxins form an interesting family of iron‐binding proteins with an almost unique fold and are highly conserved from bacteria to primates. They have a pivotal role in iron‐sulfur cluster biogenesis as regulators of the rates of cluster formation, as it is testified by the fact that frataxin absence is incompatible with life and reduced levels of the protein lead to the recessive neurodegenerative disease Friedreich's ataxia. Despite its importance, the structure of frataxin has been solved only from relatively few species. Here, we discuss the X‐ray structure of frataxin from the thermophilic fungus Chaetomium thermophilum, and the characterization of its interactions and dynamics in solution. We show that this eukaryotic frataxin has an unusual variation of the classical frataxin fold: the last helix is shorter than in other frataxins which results in a less symmetrical and compact structure. The stability of this protein is comparable to that of human frataxin, currently the most stable amongst the frataxin orthologues. We also characterized the iron‐binding mode of C. thermophilum frataxin and demonstrated that it binds it through a semi‐conserved negatively charged ridge on the first helix and beta‐strand. Moreover, this frataxin is also able to bind the bacterial ortholog of the desulfurase, which is central in iron‐sulfur cluster synthesis, and act as its inhibitor.

KW - Friedreich's ataxia

KW - iron–sulfur clusters

KW - structural biology

UR - http://www.scopus.com/inward/record.url?scp=85060798358&partnerID=8YFLogxK

U2 - 10.1111/febs.14750

DO - 10.1111/febs.14750

M3 - Article

VL - 286

SP - 495

EP - 506

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 3

ER -

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