The linker region of breast cancer resistance protein ABCG2 is critical for coupling of ATP-dependent drug transport.
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Tartalom: http://real.mtak.hu/33287/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
The linker region of breast cancer resistance protein ABCG2 is critical for coupling of ATP-dependent drug transport.
Létrehozó:
Macalou, S.
Robey, R. W.
Jabor Gozzi, G.
Shukla, S.
Grosjean, I.
Hegedűs, Tamás
Kiadó:
Birkhauser Verlag
Dátum:
2015
Téma:
QH3011 Biochemistry / biokémia
RM Therapeutics. Pharmacology / terápia, gyógyszertan
Tartalmi leírás:
The ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotide-binding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted. Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C-motif/ABC signature present in all ABC nucleotide-binding domains. Predictions of disorder and of secondary structures indicated that this C2-sequence was highly mobile and located between an alpha-helix and a loop similarly to the C-motif. Point mutations of the two first residues of the C2-sequence fully abolished the transport-coupled ATPase activity, and led to the complete loss of cell resistance to mitoxantrone. The interaction with potent, selective and non-competitive, ABCG2 inhibitors was also significantly altered upon mutation. These results suggest an important mechanistic role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux.
Nyelv:
angol
magyar
Típus:
Article
PeerReviewed
info:eu-repo/semantics/article
Formátum:
text
text
Azonosító:
Macalou, S. and Robey, R. W. and Jabor Gozzi, G. and Shukla, S. and Grosjean, I. and Hegedűs, Tamás (2015) The linker region of breast cancer resistance protein ABCG2 is critical for coupling of ATP-dependent drug transport. CELLULAR AND MOLECULAR LIFE SCIENCES, 1. pp. 1-11. ISSN 1420-682X
Kapcsolat:
MTMT:2994493; doi:10.1007/s00018-015-2118-5