Unique topology of the internal repeats in the cardiac Na+/Ca2+ exchanger.
Hydropathy analysis predicts 11 transmembrane helices in the cardiac Na+/Ca2+ exchanger. Using cysteine susceptibility analysis and epitope tagging, we here studied the membrane topology of the exchanger, in particular of the highly conserved internal alpha-1 and alpha-2 repeats. Unexpectedly, we found that the connecting loop in the alpha-1 repeat forms a re-entrant membrane loop with both ends facing the extracellular side and one residue (Asn-125) being accessible from the inside and that the region containing the alpha-2 repeat is mostly accessible from the cytoplasm. Together with other data, we propose that the exchanger may consist of nine transmembrane helices.
Iwamoto
T
T
Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Nakamura
T Y
TY
Pan
Y
Y
Uehara
A
A
Imanaga
I
I
Shigekawa
M
M
D000818:Animals; D002460:Cell Line; D004285:Dogs; D006321:Heart; D006801:Humans; D008954:Models, Biological; D016296:Mutagenesis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1