Speaker:

Jan-Philipp Machtens, Institute of Complex Systems, Zelluläre Biophysik (ICS-4)

Contents:

Glutamatergic synaptic transmission critically depends on excitatory amino acid transporters (EAATs) that remove released neurotransmitters from the synaptic cleft and thereby ensure low extracellular glutamate concentrations in the central nervous system. EAATs are thermodynamically coupled glutamate/Na⁺/H⁺/K⁺ transporters and anion-selective channels. EAAT anion channels control neuronal excitability and synaptic communication, and their physiological importance is further corroborated by the recently identified association of altered EAAT anion conduction with neurological disorders. The five mammalian EAATs differ in their effectiveness as glutamate transporters and anion channels. However, pore properties of the known isoforms such as anion selectivity and unitary current amplitudes appear to be closely similar. Although important structural information on secondary-active glutamate transport has been resolved in recent years, the molecular mechanisms underlying anion permeation are still unknown.
We performed molecular dynamics (MD) simulations of the prokaryotic EAAT homologue Glt_Ph to elucidate how these transporters conduct anions. Outward and inward-facing conformations of Glt_Ph were found to be non-conductive in MD simulations. In contrast, a lateral movement of the mobile glutamate transport domain from an intermediate conformation- together with a hydrophobic gating mechanism through voltage-promoted wetting of the pore region - led to the formation of an anion-selective conduction pathway. Our results were validated by fluorescence quenching experiments on single-tryptophane mutants of Glt_Ph and patch-clamp recordings of mammalian EAATs. Amino acid substitutions of homologous pore-forming residues have similar effects on experimental EAAT2/EAAT4 and simulated Glt_Ph single-channel conductances and anion/cation selectivities. Thus, the here identified anion conduction pathway appears to be conserved within the whole glutamate transporter family. Our results highlight how the glutamate transporter family accommodates an anion channel together with a transporter in one single protein.

Speaker:

Dr. Stefan Krieg, Jülich Supercomputing Centre

Contents:

Computing, from first principles, the hadron masses to percent accuracy, is only possible through simulations of Lattice Quantum Chromodynamics (QCD).With the advent of the present class of Pflop Machines, we now can proceed to compute per-mille effects in the particle spectrum, i.e. the proton-neutron mass difference. This difference is due to a subtle cancellation of already small effects (due to the mass difference of the up- and down-quarks and the presence of electromagnetic interactions). I will report on an ongoing project to compute this and other mass differences using simulations of Lattice QCD and Quantum Electrodynamics.

In the case of the proton and the neutron, quarks and gluons are confined to the hadron. If we, however, increase the temperature of the system sufficiently, both particles will ’melt’ and quarks and gluons behave as free particles (’quarkgluon-plasma’). This transition is described by the Equation of State (EoS) of QCD. I will discuss an ongoing project aimed at calculating the EoS including the effects of a dynamical charm quark, which is relevant for temperatures larger than 300-400 MeV.