The role of the conserved glycines of ATP-binding cassette signature motifs of MRP1 in the communication between the substrate-binding site and the catalytic centers.

The Journal of Biological Chemistry
Zsófia SzentpéteryEva Bakos

Abstract

A key element of the structural model of ABC-ATP-ases is the interaction of the two ABC domains. They complement each other's active sites in a way that the ABC signature motif (LSGGQ) of one subunit interacts with the gamma-phosphate of the ATP, bound at the Walker motifs of the opposite subunit. In the present study, the conserved glycines in the fourth position of the LSGGQ motifs of human MRP1 were substituted for aspartic acids (G771D and G1433D), the mutants were expressed in Sf9 insect cells, and the nucleotideas well as the transported substrate-protein interactions were studied. We found that these transport- and ATPase-incompetent mutants showed no nucleotide trapping under any of the conditions examined. However, when measuring the effect of nucleotide and transported substrates on the vanadate-induced cleavage reactions, we found that the effect of substrates on the cleavage reactions was significantly different in the mutant MRP1 proteins than in the wild type. Although the transported substrates (e.g. etoposide + oxidized glutathione) stimulated the formation of the posthydrolytic complex in the wild type, this reaction was inhibited in the signature mutants. Our study also revealed that a similar mutation in the ...Continue Reading

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Citations

Dec 26, 2006·Pflügers Archiv : European journal of physiology·Eva Bakos, László Homolya
Nov 8, 2011·Biochemical and Biophysical Research Communications·Krisztina FülöpAndrás Váradi
Dec 31, 2008·The Journal of General Physiology·Xiaohui WangTzyh-Chang Hwang
Sep 17, 2014·The Journal of General Physiology·Wen-Ying LinTzyh-Chang Hwang
Feb 9, 2012·Journal of Amino Acids·Rajendra PrasadManpreet Kaur Rawal
Jan 31, 2006·FEBS Letters·Annie Frelet, Markus Klein
Dec 29, 2015·Cellular and Molecular Life Sciences : CMLS·S MacalouA Di Pietro
May 22, 2010·Molecular Microbiology·Karen EhrenmanIsabelle Coppens
Apr 22, 2014·Biochimica Et Biophysica Acta·Rosa L López-MarquésMichael G Palmgren
Apr 9, 2008·Physiological Reviews·Tsung-Yu Chen, Tzyh-Chang Hwang
Jul 27, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiaohan YangJing Liang
Sep 11, 2018·Life Science Alliance·Elina Nürenberg-GoloubRobert Tampé
Dec 12, 2018·Microbiology Resource Announcements·Dexi ZhaoXueqiong Sun

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