Human recombinant mutated forms of the mitochondrial COX assembly Sco2 protein differ from wild-type in physical state and copper binding capacity
Φόρτωση...
Ημερομηνία
Συγγραφείς
Foltopoulou, P. F.
Zachariadis, G. A.
Politou, A. S.
Tsiftsoglou, A. S.
Papadopoulou, L. C.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Mol Genet Metab
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The human Sco2 protein is a cytochrome c oxidase assembly protein that participates in mitochondrial copper pathway, acting downstream of Cox17 protein. In a previous work, we detected mutations in the human SCO2 gene in three unrelated infants with fatal cardioencephalomyopathy and COX deficiency. In this study, full-length processed recombinant wild-type and two mutated forms of hSco2p (w/t-rhSco2p, E140K-rhSco2p, and S225F-rhSco2p) were produced in bacteria as soluble recombinant peptides for the first time and evaluated for differences in their physical state and ability to bind copper. Our data indicate the following: (a) w/t-rhSco2p and S225F-rhSco2p were found to be in a monomeric form in contrast to E140K-rhSco2p that was in a major non-reducible dimer and a minor monomer form; (b) wild-type and mutated rhSco2p exhibited clear differences in their physical conformational state, as shown by circular dichroism and thermal denaturation analyses; (c) copper binding studies showed that E140K-rhSco2p bound markedly less copper while S225F-rhSco2p more than expected as compared to amount of the copper bound with w/t-rhSco2p. rhCox17p served as positive control experiment. These data indicate that S225F and E140K mutations found in the SCO2 gene derived from patients alter the physical conformational state of encoded hSco2p that may disturb the normal copper transport pathway in mitochondria. These findings are valuable for understanding the molecular basis of fatal cardioencephalomyopathy and COX deficiency and for designing appropriate pharmacological interventions.
Περιγραφή
Λέξεις-κλειδιά
Amino Acid Sequence, Carrier Proteins, Cation Transport Proteins/*metabolism, Circular Dichroism, Copper/*metabolism, Dimerization, Humans, Mitochondria/*metabolism, Mitochondrial Proteins, Models, Molecular, Molecular Sequence Data, *Mutation, Protein Binding, Protein Conformation, Proteins/genetics/*metabolism, Recombinant Proteins/genetics/metabolism
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/14972329
http://ac.els-cdn.com/S1096719203002610/1-s2.0-S1096719203002610-main.pdf?_tid=e05f3c8ff97e473459db5a4cfb406c5a&acdnat=1333004718_1b827757c041d44d443daf79152de02f
http://ac.els-cdn.com/S1096719203002610/1-s2.0-S1096719203002610-main.pdf?_tid=e05f3c8ff97e473459db5a4cfb406c5a&acdnat=1333004718_1b827757c041d44d443daf79152de02f
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής