Figure 6. Proposed mechanism of calcium regulation of the mitochondrial asparate/glutamate carrier.

(a) The calcium-bound state of the aspartate/glutamate carrier dimer. On calcium binding the mobile sub-domain of EF-hands 1–2 moves to open up a hydrophobic groove in which the α-helix of the C-terminal domain (wheat) binds. Glutamate and a proton enter the carrier domain to trigger the conformational changes required for the translocation of the substrates. (b) The calcium-free state of the aspartate/glutamate carrier dimer. In the absence of calcium, the mobile sub-domain of EF-hand 1–2 closes the hydrophobic groove and the C-terminal helix is no longer bound. Instead the linker loop (red) binds to close the gap. The conformational changes may limit access of the substrates to the carrier domain. The substrate-binding site is shown as a hexagon.