Amino acid residues in transmembrane segment IX of the Na+/I- symporter play a role in its Na+ dependence and are critical for transport activity.
The Na+/I- symporter (NIS) is a key plasma membrane glycoprotein that mediates Na+-dependent active I- transport in the thyroid, lactating breast, and other tissues. The OH group of the side chain at position 354 in transmembrane segment (TMS) IX of NIS has been demonstrated to be essential for NIS function, as revealed by the study of the congenital I- transport defect-causing T354P NIS mutation. TMS IX has the most beta-OH group-containing amino acids (Ser and Thr) of any TMS in NIS. We have thoroughly characterized the functional significance of all Ser and Thr in TMS IX in NIS, as well as of other residues in TMS IX that are highly conserved in other transporters of the SLC5A protein family. Here we show that five beta-OH group-containing residues (Thr-351, Ser-353, Thr-354, Ser-356, and Thr-357) and Asn-360, all of which putatively face the same side of the helix in TMS IX, plus Asp-369, located in the membrane/cytosol interface, play key roles in NIS function and seem to be involved in Na+ binding/translocation.
De la Vieja
Antonio
A
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Reed
Mia D
MD
Ginter
Christopher S
CS
Carrasco
Nancy
N
D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D020125:Mutation, Missense; D009928:Organ Specificity / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D006023:Glycoproteins; D007455:Iodine; D012964:Sodium; D027981:Symporters; D000099209:Sodium-Iodide Symporters