Energy Landscape of the Substrate Translocation Equilibrium of Plasma-Membrane Glutamate Transporters

• DOI: 10.1021/acs.jpcb.7b09059
• Publication Date: 2017-12-08T12:41:55Z
• Authors: Jiali Wang; Thomas Albers; Christof Grewer
• Keywords: Electrostatics

Glutamate transporters maintain a large glutamate concentration gradient across synaptic membranes and are, thus, critical for functioning of the excitatory synapse. Mammalian concentrate inside cells through energetic coupling flux to transmembrane Na+. Structural models based on an archeal homologue, GltPh, suggest elevator-like carrier mechanism. However, determinants this carrier-based movement are not well understood. Although electrostatics play important role in governing these energetics, their implication transport dynamics has been studied. Here, we combine pre-steady-state kinetic analysis translocation equilibrium with electrostatic computations gain insight into energetics process. Our results show biphasic nature translocation, consistent existence intermediate pathway. In absence voltage, is shifted outward-facing configuration. Electrostatic confirm state that energetically feasible presence bound Na+ ions, whereas substrate-hopping model prohibitive. highlight contribution charge compensation add from previous molecular simulations improved understanding