Identification of a structural requirement for thyroid Na+/I− symporter (NIS) function from analysis of a mutation that causes human congenital hypothyroidism

FEBS Letters

Levy, Orlie¹  Ginter, Christopher S¹  Levy, Daniel¹  De la Vieja, Antonio¹  Carrasco, Nancy¹ 

[1] Albert Einstein College of Medicine, Department of Molecular Pharmacology, 1300 Morris Park Avenue, Bronx, NY 10461, USA

关键词: Na+/I− symporter;    Congenital hypothyroidism;    Iodide;    Transport;    Thyroid;   

DOI  :  10.1016/S0014-5793(98)00522-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 [1, 2]. 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 β-carbon of the amino acid residue at position 354. Hence, this hydroxyl group is essential for NIS function.

【 授权许可】

Unknown