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dc.contributor.author
Ferrandino, Giuseppe
dc.contributor.author
Nicola, Juan Pablo
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dc.contributor.author
Sánchez, Yuly E.
dc.contributor.author
Echeverria, Ignacia
dc.contributor.author
Liu, Yunlong
dc.contributor.author
Amzel, Mario
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dc.contributor.author
Carrasco, Nancy
dc.date.available
2018-06-06T18:03:36Z
dc.date.issued
2016-09
dc.identifier.citation
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
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/47517
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Sodium/Iodide Symporter
dc.subject
Stoichiometry
dc.subject
Sodium Binding Site
dc.subject
Protein Dynamics
dc.subject.classification
Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Na+ coordination at the Na2 site of the Na+/I- symporter
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-05-29T20:56:32Z
dc.identifier.eissn
1091-6490
dc.journal.volume
113
dc.journal.number
37
dc.journal.pagination
E5379-E5388
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Washington
dc.description.fil
Fil: Ferrandino, Giuseppe. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Nicola, Juan Pablo. University of Yale. School of Medicine; Estados Unidos. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Sánchez, Yuly E.. University Johns Hopkins. Dept.of Chemistry; Estados Unidos
dc.description.fil
Fil: Echeverria, Ignacia. University Johns Hopkins. Dept.of Chemistry; Estados Unidos
dc.description.fil
Fil: Liu, Yunlong. University Johns Hopkins. Dept.of Chemistry; Estados Unidos
dc.description.fil
Fil: Amzel, Mario. University Johns Hopkins. Dept.of Chemistry; Estados Unidos
dc.description.fil
Fil: Carrasco, Nancy. University of Yale. School of Medicine; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/113/37/E5379
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1607231113
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