Artículo
Na+ coordination at the Na2 site of the Na+/I- symporter
Ferrandino, Giuseppe; Nicola, Juan Pablo
; Sánchez, Yuly E.; Echeverria, Ignacia; Liu, Yunlong; Amzel, Mario; Carrasco, Nancy
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
09/2016
Editorial:
National Academy of Sciences
Revista:
Proceedings of the National Academy of Sciences of The United States of America
ISSN:
0027-8424
e-ISSN:
1091-6490
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid-the first step in thyroid hormone biosynthesis-with a 2 Na(+): 1 I(-) stoichiometry. The two Na(+) binding sites (Na1 and Na2) and the I(-) binding site interact allosterically: when Na(+) binds to a Na(+) site, the affinity of NIS for the other Na(+) and for I(-) increases significantly. In all Na(+)-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na(+) ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues-S66, D191, Q194, and Q263-are also involved in Na(+) coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I(-) These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance.
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Identificadores
Colecciones
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Ferrandino, Giuseppe; Nicola, Juan Pablo; Sánchez, Yuly E.; Echeverria, Ignacia; Liu, Yunlong; et al.; Na+ coordination at the Na2 site of the Na+/I- symporter; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 113; 37; 9-2016; E5379-E5388
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