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Role of the Q‐loop region in function of the DrrAB transporter of Streptomyces peucetius.
Author(s) -
Rao Divya K,
Kaur Parjit
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb22-c
Subject(s) - atp binding cassette transporter , cyclic nucleotide binding domain , transmembrane domain , transporter , multiple drug resistance , transmembrane protein , abcc1 , p glycoprotein , biochemistry , function (biology) , protein subunit , chemistry , nucleotide , biology , microbiology and biotechnology , gene , receptor , antibiotics
ATP binding cassette (ABC) transporters constitute one of the largest families of transport proteins. These membrane bound pumps are of biomedical significance as they are associated with diseases such as cystic fibrosis. The occurrence of multidrug resistance (MDR) in human cancer cells has been correlated with the over expression of human ABC transporters namely P‐glycoprotein (Pgp), multidrug resistance associated protein (MRP1) and breast cancer resistance protein (BCRP). The present study analyzes the role of the Q‐loop region in function of the DrrAB transporter of Streptomyces peucetius. In DrrAB, the nucleotide‐binding domain (NBD) and transmembrane domain (TMD) are present on separate subunits, DrrA and DrrB respectively. Such architecture makes it possible to easily study NBD: NBD and NBD: TMD interactions. This study provides evidence for the role of Q‐loop in dimerization of the NBD’s and in subunit interactions between NBD and TMD. By cross‐linking and ATPγS binding assays, we show that Q‐loop is present at the interface of the NBD dimers which are induced on nucleotide binding. By fourier resonance energy transfer assays, we show a head‐to‐tail conformation of DrrA dimers. The Q‐loop also seems to participate in the interaction with the transmembrane domain of DrrB. Thus, the present study is the first biochemical report showing direct involvement of Q‐loop in dimerization of NBD and its possible interaction with the TMD.