title: Identification of a structural requirement for thyroid Na+/I- symporter (NIS) function from analysis of a mutation that causes human congenital hypothyroidism.
abstract: Patients with congenital lack of I transport do not accumulate I in their thyroids, often resulting in severe hypothyroidism. A single amino acid substitution in the thyroid Na+/I- symporter (NIS), proline replacing threonine at position 354 (T354P), was recently identified as the cause of this condition in two independent patients. Here we report that the lack of I- transport activity in T354P NIS generated by site-directed mutagenesis, is not due to a structural change induced by proline, but rather to the absence of a hydroxyl group at the beta-carbon of the amino acid residue at position 354. Hence, this hydroxyl group is essential for NIS function.
authors.affiliation: Albert Einstein College of Medicine, Department of Molecular Pharmacology, Bronx, NY 10461, USA.
authors.forename: O
authors.initials: O
authors.lastname: Levy
authors.forename: C S
authors.initials: CS
authors.lastname: Ginter
authors.forename: A
authors.initials: A
authors.lastname: De la Vieja
authors.forename: D
authors.initials: D
authors.lastname: Levy
authors.forename: N
authors.initials: N
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007455:Iodine / Q000378:metabolism*; D017136:Ion Transport; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D027981:Symporters; D000099209:Sodium-Iodide Symporters
chemical_list: D002352:Carrier Proteins; D007455:Iodine; D008565:Membrane Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters