Drosophila melanogaster frataxin: protein crystal and predicted solution structure with identification of the iron-binding regions.
Drosophila melanogaster
Friedreich's ataxia
ISC pathway
frataxin
iron–sulfur clusters
Journal
Acta crystallographica. Section D, Structural biology
ISSN: 2059-7983
Titre abrégé: Acta Crystallogr D Struct Biol
Pays: United States
ID NLM: 101676043
Informations de publication
Date de publication:
01 Jan 2023
01 Jan 2023
Historique:
received:
07
09
2022
accepted:
03
12
2022
pmc-release:
01
01
2024
entrez:
5
1
2023
pubmed:
6
1
2023
medline:
7
1
2023
Statut:
ppublish
Résumé
Friedreich's ataxia (FRDA) is a hereditary cardiodegenerative and neurodegenerative disease that affects 1 in 50 000 Americans. FRDA arises from either a cellular inability to produce sufficient quantities or the production of a nonfunctional form of the protein frataxin, a key molecule associated with mitochondrial iron-sulfur cluster biosynthesis. Within the mitochondrial iron-sulfur cluster (ISC) assembly pathway, frataxin serves as an allosteric regulator for cysteine desulfurase, the enzyme that provides sulfur for [2Fe-2S] cluster assembly. Frataxin is a known iron-binding protein and is also linked to the delivery of ferrous ions to the scaffold protein, the ISC molecule responsible for the direct assembly of [2Fe-2S] clusters. The goal of this report is to provide structural details of the Drosophila melanogaster frataxin ortholog (Dfh), using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, in order to provide the foundational insight needed to understand the structure-function correlation of the protein. Additionally, NMR iron(II) titrations were used to provide metal contacts on the protein to better understand how it binds iron and aids its delivery to the ISC scaffold protein. Here, the structural and functional similarities of Dfh to its orthologs are also outlined. Structural data show that bacterial, yeast, human and Drosophila frataxins are structurally similar, apart from a structured C-terminus in Dfh that is likely to aid in protein stability. The iron-binding location on helix 1 and strand 1 of Dfh is also conserved across orthologs.
Identifiants
pubmed: 36601804
pii: S2059798322011639
doi: 10.1107/S2059798322011639
pmc: PMC9815096
doi:
Substances chimiques
Iron-Binding Proteins
0
Iron
E1UOL152H7
Sulfur
70FD1KFU70
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22-30Subventions
Organisme : American Heart Association
ID : 12PRE11720005
Organisme : NIDDK NIH HHS
ID : DK068139
Pays : United States
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