Publications

Citation

BibTex format

@article{Rosenberg:2015:10.1107/S1399004715010676,
author = {Rosenberg, MF and Bikadi, Z and Hazai, E and Starborg, T and Kelley, L and Chayen, N and Ford, RC and Mao, Q},
doi = {10.1107/S1399004715010676},
journal = {Acta Crystallographica Section D - Biological Crystallography},
pages = {1725--1735},
title = {Three-dimensional structure of the human breast cancer resistance protein (BCRP/ABCG2) in an inward-facing conformation},
url = {http://dx.doi.org/10.1107/S1399004715010676},
volume = {71},
year = {2015}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ABCG2 is an efflux drug transporter that plays an important role in drug resistance and drug disposition. In this study, the first three-dimensional structure of human full-length ABCG2 analysed by electron crystallography from two-dimensional crystals in the absence of nucleotides and transported substrates is reported at 2 nm resolution. In this state, ABCG2 forms a symmetric homodimer with a noncrystallographic twofold axis perpendicular to the two-dimensional crystal plane, as confirmed by subtomogram averaging. This configuration suggests an inward-facing configuration similar to murine ABCB1, with the nucleotide-binding domains (NBDs) widely separated from each other. In the three-dimensional map, densities representing the long cytoplasmic extensions from the transmembrane domains that connect the NBDs are clearly visible. The structural data have allowed the atomic model of ABCG2 to be refined, in which the two arms of the V-shaped ABCG2 homodimeric complex are in a more closed and narrower conformation. The structural data and the refined model of ABCG2 are compatible with the biochemical analysis of the previously published mutagenesis studies, providing novel insight into the structure and function of the transporter.Keywords: ABCG2; BCRP; ABC transporter; ATP-binding cassette transporter; cryo-electron microscopy; three-dimensional structure from two-dimensional crystals.
AU  - Rosenberg,MF
AU  - Bikadi,Z
AU  - Hazai,E
AU  - Starborg,T
AU  - Kelley,L
AU  - Chayen,N
AU  - Ford,RC
AU  - Mao,Q
DO  - 10.1107/S1399004715010676
EP  - 1735
PY  - 2015///
SN  - 0907-4449
SP  - 1725
TI  - Three-dimensional structure of the human breast cancer resistance protein (BCRP/ABCG2) in an inward-facing conformation
T2  - Acta Crystallographica Section D - Biological Crystallography
UR  - http://dx.doi.org/10.1107/S1399004715010676
UR  - http://hdl.handle.net/10044/1/25598
VL  - 71
ER  -

Download

Citation

BibTex format

RIS format (EndNote, RefMan)

Centre for Structural Biology Open Day

Useful Links

Structural Biology