Aspartate 338 contributes to the cationic specificity and to driver-amino acid coupling in the insect cotransporter KAAT1
Articolo
Data di Pubblicazione:
2004
Citazione:
Aspartate 338 contributes to the cationic specificity
and to driver-amino acid coupling in the insect
cotransporter KAAT1 / S.A Mari, A. Soragna, M. Castagna, E. Bossi, A. Peres, V.F. Sacchi. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - 61:12(2004), pp. 243-256.
Abstract:
To investigate the peculiar ionic specificity of
KAAT1, an Na+- and K+-coupled amino acid cotransporter
from Lepidoptera, a detailed analysis of membrane topology
predictions was performed, together with sequence
comparison with strictly Na+-dependent mammalian cotransporters
from the same family. The analysis identified
aspartate 338, a residue present also in the other cotransporter
accepting K+ (CAATCH1), but absent in most mammalian
transporters that have, instead, an asparagine in the
corresponding position. Mutation of D338 in KAAT1 led
either to non-functional transporters (D338G, D338C), or
to an altered ionic selectivity (D338E, D338N), observable
in uptake experiments and in electrophysiological properties.
In particular, in D338E, the transport activity, while
persisting in the presence of Na+, appeared to be completely
abolished in the presence of K+. D338E also
showed uncoupling between transport-associated current
and uptake. The opposite mutation in the g-aminobutyric
acid transporter rGAT-1 (N327D) resulted in complete loss
of function. In conclusion, aspartate 338 in KAAT1 appears
to be important in allowing K+, in addition to Na+, to
drive the transport mechanism, although other residues in
different parts of the protein may also play a role in the
complete determination of ionic selectivity.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S.A Mari, A. Soragna, M. Castagna, E. Bossi, A. Peres, V.F. Sacchi
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