TCB Publications - Abstract
Zhijian Huang and Emad Tajkhorshid. Dynamics of the extracellular gate and ion-substrate coupling in the glutamate transporter. Biophysical Journal, 95:2292-2300, 2008. (PMC: 2517027)
binding sites, and the mechanism of cotransport of Na ions, using molecular dynamics simulations of a membrane-embedded
model of GluT in its apo (empty form) and various Na- and/or substrate-bound states. The results shed light on the
mechanism of the extracellular gate and on the sequence of binding of the substrate and Na ions to GluT during the transport
cycle. The results suggest that the helical hairpin HP2 plays the key role of the extracellular gate for the substrate binding site,
and that the opening and closure of the gate is controlled by substrate binding. GluT adopts an open conformation in the
absence of the substrate exposing the binding sites of the substrate and Na ions to the extracellular solution. Based on the
calculated trajectories, we propose that Na1 is the first element to bind GluT, as it is found to be important for the completion of
the substrate binding site. The subsequent binding of the substrate, in turn, is shown to result in an almost complete closure of
the extracellular gate and the formation of the Na2 binding site. Finally, binding of Na2 locks the extracellular gate and
completes the formation of the occluded state of GluT.
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