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Topology model of Na + /dicarboxylate cotransporter 1
Author(s) -
Joshi Aditya D.,
Pajor Ana M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a530-d
Subject(s) - cotransporter , transmembrane domain , transporter , homology modeling , chemistry , symporter , transmembrane protein , biochemistry , membrane , gene , enzyme , receptor , organic chemistry , sodium
The absorption of Tricarboxylic Acid Cycle intermediates, such as succinate and citrate, across the apical membrane of the kidney proximal tubule and the small intestine is mediated by the Na + /dicarboxylate cotransporter 1 (NaDC1). NaDC1 is a low affinity transporter that belongs to the SLC13 gene family. The previous secondary structure model of NaDC1 contained 11 transmembrane helices (TM) but a 13 TM structure is predicted from homology‐based modeling. The aim of this study is to test the validity of the new 13 TM model of rabbit NaDC1. Individual cysteines were introduced in putative extracellular and intracellular loops of the transporter by site‐directed mutagenesis. The membrane impermeable reagent, MTSEA‐Biotin (N‐biotinylaminoethyl methanethiosulfonate), was used to covalently label the cysteine residues. Our data support possibility of 13 transmembrane helices but the positions of TM 1 to 4 resemble the old 11 TM model. The position of helices in the C‐terminal half of the transporter (TM 5 to 13) are in agreement with the new 13 TM model. Hence our initial results support the 13 TM model for rbNaDC1 cotransporter. (This work is supported by NIH grant DK46269).