Refine
Year of publication
Document Type
- Preprint (603)
- Article (296)
- Doctoral Thesis (2)
Has Fulltext
- yes (901)
Is part of the Bibliography
- no (901)
Keywords
- Heavy Ion Experiments (19)
- Hadron-Hadron scattering (experiments) (11)
- Hadron-Hadron Scattering (9)
- Heavy-ion collision (5)
- LHC (4)
- Quark-Gluon Plasma (4)
- Collective Flow (3)
- Jets and Jet Substructure (3)
- ALICE (2)
- Charm physics (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Heavy Ions (2)
- Heavy Quark Production (2)
- Jets (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Particle Correlations and Fluctuations (2)
- Particle correlations and fluctuations (2)
- 900 GeV (1)
- ACURATE neo (1)
- ALICE experiment (1)
- Beauty production (1)
- Boosted Jets (1)
- Centrality Class (1)
- Centrality Selection (1)
- Chloroxospezies (1)
- Desinfektionsmittel (1)
- Electron-pion identification (1)
- Electroweak interaction (1)
- Elektrochemie (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- HBT (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hard Scattering (1)
- Heavy Ion Experiment (1)
- Heavy ions (1)
- Heavy-flavour production (1)
- Heavy-ion collisions (1)
- Intensity interferometry (1)
- Invariant Mass Distribution (1)
- Ionisation energy loss (1)
- Jet Physics (1)
- Jet Substructure (1)
- Material budget (1)
- Minimum Bias (1)
- Monte Carlo (1)
- Multi-Parton Interactions (1)
- Multi-wire proportional drift chamber (1)
- Neural network (1)
- Nuclear modification factor (1)
- PYTHIA (1)
- Particle and Resonance Production (1)
- Particle and resonance production (1)
- Pb–Pb (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- QCD (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quarkonium (1)
- Rapidity Range (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Resolution Parameter (1)
- Single electrons (1)
- Systematic Uncertainty (1)
- TAVR (1)
- TR (1)
- Time Projection Chamber (1)
- Tracking (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Trigger (1)
- Vector Boson Production (1)
- Viologene (1)
- Xenon-based gas mixture (1)
- aging (1)
- aortic stenosis (1)
- dE/dx (1)
- detector (1)
- experimental results (1)
- genes for longevity (1)
- heavy ion experiments (1)
- pp collisions (1)
- quark gluon plasma (1)
- senescence (1)
- signal transduction (1)
- transcatheter aortic valve replacement (1)
- transfemoral (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (896)
- Frankfurt Institute for Advanced Studies (FIAS) (825)
- Informatik (791)
- Informatik und Mathematik (3)
- Medizin (3)
- Hochschulrechenzentrum (2)
- Biochemie, Chemie und Pharmazie (1)
- Biowissenschaften (1)
ATP-binding cassette (ABC) transporters shuttle diverse substrates across biological membranes. They play a role in many physiological processes but are also the reason for antibiotic resistance of microbes and multi drug resistance in cancer, and their dysfunction can lead to serious diseases. Transport is achieved through an ATP-driven closure of the two nucleotide binding sites (NBSs) which induces a transition between an inward-facing (IF) and an outward-facing (OF) conformation of the connected transmembrane domains (TMDs). In contrast to this forward transition, the reverse transition (OF-to-IF) that involves Mg2+-dependent ATP hydrolysis and release is less understood. This is particularly relevant for heterodimeric ABC transporters with asymmetric NBSs. These transporters possess an ATPase active consensus NBS (c-NBS) and a degenerate NBS (d-NBS) with little or no ATPase activity.
Crucial details regarding function and mechanism of the transport cycle remain elusive.
Here, these open questions were addressed using pulse electron-electron double resonance (PELDOR or DEER) spectroscopy of the heterodimeric ABC exporter TmrAB.
To better understand the transport cycle, the underlying kinetics of the conformational transitions need to be elucidated. By introducing paramagnetic nitroxide (NO) spin probes at key positions of TmrAB and employing time-resolved PELDOR spectroscopy, the forward transition could be followed over time and the rate constants for the conformational transition at the TMDs and NBSs were characterized.
The temperature dependence of these rate constants was further analyzed to determine for the first time the activation energy of conformational changes in a large membrane protein. For TMD opening and c-NBS dimerization, values of 75 ± 27 kJ/mol and 56 ± 3 kJ/mol, respectively were found. These values agree with reported activation energies of peptide transport and peptide dissociation in other ABC transporters, suggesting that the forward transition may be the rate-limiting step for substrate translocation.
The functional relevance of asymmetric NBSs is so far not well understood. By combining Mg2+-to-Mn2+ substitution with Mn2+-NO and NO-NO PELDOR spectroscopy, the binding of ATP-Mn2+, the conformation of the NBSs, and the conformation of the TMDs could be simultaneously monitored for the first time. These results reveal an asymmetric post-hydrolytic state. Time-resolved investigation showed that ATP hydrolysis at the active c-NBS triggers the reverse transition, whereas opening of the impaired d-NBS regulates the return to the IF conformation.