bcrp - publications

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1. Biochemistry. 2012 Apr 12. [Epub ahead of print]

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

Mo W, Qi J, Zhang JT.

ABCG2 is a member of the ATP-binding cassette transporter superfamily and its
over-expression 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 of homo-oligomers consisting of
possibly 8-12 subunits and the oligomerization domain was mapped to the
C-terminal domain including TM5-ECL3-TM6. In this study, we further investigated
this domain in detail for the role of each segment in 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 TM5-ECL3-TM6 plays distinctive roles in
oligomerization and function of ABCG2.

PMID: 22497316 [PubMed - as supplied by publisher]