The Possible Role of 94-125 Peptide Fragment of Histone H2B in Nickel-Induced Carcinogenesis
Φόρτωση...
Ημερομηνία
Συγγραφείς
Nunes, A. M.
Zavitsanos, K.
Del Conte, R.
Malandrinos, G.
Hadjiliadis, N.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
American Chemical Society
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Inorg Chem
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The molecular mechanism by which nickel carcinogenicity is exerted is not fully understood. However, it is believed to involve DNA damage and epigenetic effects in chromatin, resulting from metal binding to the cell nucleus. Histone nuclear proteins are the major candidates for metal binding not only due to their abundance but also due to the presence of strong binding sites within their sequence. In order to investigate the binding capacity of histone H2B toward Ni(2+) ions, we synthesized the peptide Ac-IQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK-Am (H2B(94-125)) as a model of the C-terminal tail. Complexation of H2B(94-125) with Ni(2+) starts at pH around 5 with the formation of a distorted octahedral complex. Over pH 8, this species shifts to a square-planar geometry, with the complete consumption of free Ni(2+) ions at pH 10. The formation of the diamagnetic square-planar complex was further studied by means of NMR spectroscopy. On the basis of the NOE connectivities we determined a well-resolved solution structure for the binding site of the H2B(94-125)-Ni(2+) complex, including residues E(12)LAKHAVS(19). Interestingly, nickel binding strongly affects the C-terminal of the peptide, forcing it to approach the coordination plane. If such a structural alteration is able to occur under physiological conditions, it is highly possible that it interferes with the histone's physiological role and particularly with the ubiquitination process, taking place at Lys(120). We believe that these findings will assist in a better understanding of the role of histone H2B in the mechanisms of metal-induced toxicity and carcinogenesis.
Περιγραφή
Λέξεις-κλειδιά
protein secondary structure, cytochrome-c-oxidase, metal-binding sequence, chemical-shift index, crystal-structure, terminal peptide, ni(ii) ions, coordination properties, magnetic-resonance, nmr-spectroscopy
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000278615700045
http://pubs.acs.org/doi/pdfplus/10.1021/ic1005665
http://pubs.acs.org/doi/pdfplus/10.1021/ic1005665
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας