Conformational dynamics and regulation of bacterial type I maltose ABC transporters

• Applicants: Professorin Dr. Enrica Bordignon; Professor Dr. Erwin Schneider
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2010 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 163317791

ATP-binding cassette (ABC) transporters are membrane proteins that mediate the uptake or export of an enormous variety of substrates at the expense of ATP. ABC transporters share a common structural organization comprising two transmembrane domains that form the translocation pore and two nucleotide-binding domains that hydrolyse ATP. The maltose transporter of E. coli/Salmonella has served as the model for canonical ABC import systems which require an additional component, a substrate-specific binding protein for function. Based on a plethora of genetic, biochemical and structural data we propose to investigate the dynamics of the system in detail. To this end, we will combine site-specific chemical crosslinking with electron paramagnetic resonance spectroscopy to identify individual steps of the transport cycle. The results, together with molecular modelling will eventually lead to a complete picture of the transporter’s motional changes and thus to the understanding of the transport mechanism at the molecular level. Furthermore, we will address by the same techniques completed by fluorescence-based technology (FP-FRET, FCS), the physiologically relevant question of the mechanism by which the glucose transporter component, EIIAGlc, inhibits the maltose transporter in a process termed ‘inducer exclusion’.

• DFG Programme: Research Grants