Format

Send to

Choose Destination
Biochemistry. 2012 May 1;51(17):3634-41. doi: 10.1021/bi300301a. Epub 2012 Apr 19.

Different roles of TM5, TM6, and ECL3 in the oligomerization and function of human ABCG2.

Author information

1
Department of Pharmacology and Toxicology and IU Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.

Abstract

ABCG2 is a member of the ATP-binding cassette transporter superfamily, and its overexpression causes multidrug resistance (MDR) in cancer chemotherapy. ABCG2 may also protect cancer stem cells by extruding cytotoxic materials. ABCG2 has previously been shown to exist as a high-order homo-oligomer consisting of possibly 8-12 subunits, and the oligomerization domain was mapped to the C-terminal domain, including TM5, ECL3, and TM6. In this study, we further investigate this domain in detail for the role of each segment in the oligomerization and drug transport function of ABCG2 using domain swapping and site-directed mutagenesis. We found that none of the three segments (TM5, TM6, and ECL3) is essential for the oligomerization activity of ABCG2 and that any one of these three segments in the full-length context is sufficient to support ABCG2 oligomerization. While TM5 plays an important role in the drug transport function of ABCG2, TM6 and ECL3 are replaceable. Thus, each segment in the TM5-ECL3-TM6 domain plays a distinctive role in the oligomerization and function of ABCG2.

PMID:
22497316
DOI:
10.1021/bi300301a
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center