Interaction of the nucleotide binding domains and regulation of the ATPase activity of the human retina specific ABC transporter, ABCR

Biochemistry
Esther E Biswas-Fiss

Abstract

We report here a novel regulation of the ATPase activity of the human retina specific ATP binding cassette transporter (ABC), ABCR, by nucleotide binding domain interactions. We also present evidence that recombinant nucleotide binding domains of ABCR interact in vitro in the complete absence of transmembrane domains (TMDs). Although similar domain-domain interactions have been described in other ABC transporters, the roles of such interactions on the enzymatic mechanisms of these transporters have not been demonstrated experimentally. A quantitative analysis of the in vitro interactions as a function of the nucleotide-bound state demonstrated that the interaction takes place in the absence of nucleotide as well as in the presence of ATP and that it only attenuates in the ADP-bound state. Analysis of the ATPase activities of these proteins in free and complex states indicated that the NBD1-NBD2 interaction significantly influences the ATPase activity. Further investigation, using site-specific mutants, showed that mutations in NBD2 but not NBD1 led to the alteration of the ATPase activity of the NBD1.NBD2 complex and residue Arg 2038 is critical to this regulation. These data indicate that changes in the oligomeric state of the...Continue Reading

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Citations

Apr 21, 2010·The Journal of Biological Chemistry·Esther E Biswas-FissSubhasis B Biswas
Feb 12, 2008·Investigative Ophthalmology & Visual Science·Ambarish S PawarDavid R Pepperberg
Mar 4, 2014·Protein Expression and Purification·Yaroslav Tsybovsky, Krzysztof Palczewski
Jul 17, 2010·Progress in Lipid Research·Robert S Molday, Kang Zhang
Jun 15, 2007·The FEBS Journal·Heidi de WetFrances M Ashcroft
Jun 19, 2007·Biochimica Et Biophysica Acta·Jean-Pierre GilletJosé Remacle
Oct 13, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Xianchao PanHu Mei
Oct 3, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T CroninO Adjali

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