Mechanism and putative structure of B 0 -like neutral amino acid transporters

Abstract

The Na+-dependent transport of neutral amino acids in epithelial cells and neurons is mediated by B0-type neutral amino acid transporters. Two B0-type amino acid transporters have been identified in the neurotransmitter transporter family SLC6, namely B 0AT1 (SLC6A19) and B0AT2 (SLC6A15). In contrast to other members of this family, B0-like transporters are chloride- independent. B0AT1 and B0AT2 preferentially bind the substrate prior to the Na+-ion. The Na+-concentration affects the Km of the substrate and vice versa. A kinetic scheme is proposed that is consistent with the experimental data. An overlapping binding site of substrate and cosubstrate has been demonstrated in the bacterial orthologue LeuTAa from Aquifex aeolicus, which elegantly explains the mutual effect of substrate and cosubstrate on each other's Km-value. LeuTAa is sequence-related to transporters of the SLC6 family, allowing homology modeling of B0-like transporters along its structure. Show more