Characterization of human frataxin missense variants in cancer tissues.
cancer tissues
human frataxin
missense variants
protein folding
protein stability
protein variants
single amino acid substitution
somatic mutations
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
14
01
2019
revised:
17
04
2019
accepted:
06
05
2019
pubmed:
11
5
2019
medline:
14
3
2020
entrez:
11
5
2019
Statut:
ppublish
Résumé
Human frataxin is an iron-binding protein involved in the mitochondrial iron-sulfur (Fe-S) clusters assembly, a process fundamental for the functional activity of mitochondrial proteins. Decreased level of frataxin expression is associated with the neurodegenerative disease Friedreich ataxia. Defective function of frataxin may cause defects in mitochondria, leading to increased tumorigenesis. Tumor-initiating cells show higher iron uptake, a decrease in iron storage and a reduced Fe-S clusters synthesis and utilization. In this study, we selected, from COSMIC database, the somatic human frataxin missense variants found in cancer tissues p.D104G, p.A107V, p.F109L, p.Y123S, p.S161I, p.W173C, p.S181F, and p.S202F to analyze the effect of the single amino acid substitutions on frataxin structure, function, and stability. The spectral properties, the thermodynamic and the kinetic stability, as well as the molecular dynamics of the frataxin missense variants found in cancer tissues point to local changes confined to the environment of the mutated residues. The global fold of the variants is not altered by the amino acid substitutions; however, some of the variants show a decreased stability and a decreased functional activity in comparison with that of the wild-type protein.
Identifiants
pubmed: 31074541
doi: 10.1002/humu.23789
pmc: PMC6744310
mid: NIHMS1029142
doi:
Substances chimiques
Iron-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1400-1413Subventions
Organisme : NHGRI NIH HHS
ID : R13 HG006650
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG007346
Pays : United States
Organisme : NIH HHS
ID : NIH U41 HG007446
Pays : United States
Organisme : NIH HHS
ID : NIH R13 HG006650
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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