Thermodynamic Basis for Conformational Coupling in an ATP-Binding Cassette Exporter.

ATP-binding cassette (ABC) transporters constitute one of the largest protein superfamilies, and they mediate the transport of diverse substrates across the membrane. The molecular mechanism for transducing the energy from ATP binding and hydrolysis into the conformational changes remains elusive. Here, we determined the thermodynamics underlying the ATP-induced global conformational switching for the ABC exporter TmrAB using temperature-resolved pulsed electron-electron double resonance (PELDOR or DEER) spectroscopy.

In situ observation of conformational dynamics and protein ligand-substrate interactions in outer-membrane proteins with DEER/PELDOR spectroscopy.

Observation of structure and conformational dynamics of membrane proteins at high resolution in their native environments is challenging because of the lack of suitable techniques. We have developed an approach for high-precision distance measurements in the nanometer range for outer-membrane proteins (OMPs) in intact Escherichia coli and native membranes. OMPs in Gram-negative bacteria rarely have reactive cysteines.

Conformational Coupling and trans-Inhibition in the Human Antigen Transporter Ortholog TmrAB Resolved with Dipolar EPR Spectroscopy.

ATP-binding cassette (ABC) exporters actively move chemically diverse substrates across biological membranes. Their malfunction leads to human diseases. Many ABC exporters encompass asymmetric nucleotide-binding sites (NBSs), and some of them are inhibited by the transported substrate.

Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP.

ABC transporters form one of the largest protein superfamilies in all domains of life, catalyzing the movement of diverse substrates across membranes. In this key position, ABC transporters can mediate multidrug resistance in cancer therapy and their dysfunction is linked to various diseases. Here, we describe the 2.