The uncoupled ATPase activity of the ABC transporter BtuC2D2 leads to a hysteretic conformational change, conformational memory, and improved activity

Scientific Reports
Nurit Livnat-LevanonOded Lewinson

Abstract

ABC transporters comprise a large and ubiquitous family of proteins. From bacteria to man they translocate solutes at the expense of ATP hydrolysis. Unlike other enzymes that use ATP as an energy source, ABC transporters are notorious for having high levels of basal ATPase activity: they hydrolyze ATP also in the absence of their substrate. It is unknown what are the effects of such prolonged and constant activity on the stability and function of ABC transporters or any other enzyme. Here we report that prolonged ATP hydrolysis is beneficial to the ABC transporter BtuC2D2. Using ATPase assays, surface plasmon resonance interaction experiments, and transport assays we observe that the constantly active transporter remains stable and functional for much longer than the idle one. Remarkably, during extended activity the transporter undergoes a slow conformational change (hysteresis) and gradually attains a hyperactive state in which it is more active than it was to begin with. This phenomenon is different from stabilization of enzymes by ligand binding: the hyperactive state is only reached through ATP hydrolysis, and not ATP binding. BtuC2D2 displays a strong conformational memory for this excited state, and takes hours to return...Continue Reading

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Citations

Jan 21, 2017·Journal of Molecular Biology·Oded Lewinson, Nurit Livnat-Levanon
Nov 21, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Razvan C StanMaristela M de Camargo
Aug 21, 2016·Biological Chemistry·Manuel WagnerLutz Schmitt
Jun 20, 2018·Nature Chemical Biology·Min YangOded Lewinson
Jan 24, 2017·PLoS Pathogens·Adi HaberAnat A Herskovits
Feb 8, 2018·Biochimica Et Biophysica Acta. Biomembranes·Atanu BanerjeeRajendra Prasad

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Methods Mentioned

BETA
size exclusion chromatography
protein assay
biosensor
chip
gel filtration

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