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Identification of a chloride ion binding site in Na+/Cl -dependent transporters.

Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Research Abstract Details 

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  • Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Abstract Text:

    lucy r forrestLucy R Forrest,sotiria tavoulariSotiria Tavoulari,yuan-wei zhangYuan-Wei Zhang,gary rudnickGary Rudnick,barry honigBarry Honig,

    The recent determination of the crystal structure of the leucine transporter from Aquifex aeolicus (aaLeuT) has provided significant insights into the function of neurotransmitter:sodium symporters. Transport by aaLeuT is Cl(-) independent, whereas many neurotransmitter:sodium symporters from higher organisms depend on Cl(-) ions. However, the only Cl(-) ion identified in the aaLeuT structure interacts with nonconserved residues in extracellular loops, and thus the relevance of this binding site is unclear. Here, we use calculations of pK(A)s and homology modeling to predict the location of a functionally important Cl(-) binding site in serotonin transporter and other Cl(-)-dependent transporters. We validate our model through the site-directed mutagenesis of residues predicted to coordinate the Cl(-) ion and through the observation of sequence conservation patterns in other Cl(-)-dependent transporters. The proposed site is located midway across the membrane and is formed by residues from transmembrane helices 2, 6, and 7. It is close to the Na1 sodium binding site, thus providing an explanation for the coupling of Cl(-) and Na(+) ions during transport. Other implications of the model are also discussed.

    Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Publishing Authors By Initials

    lr forrestLR Forrest,s tavoulariS Tavoulari,yw zhangYW Zhang,g rudnickG Rudnick,b honigB Honig,

    For similar inorganic chemicals: electrolytes: ions: cations: cations, monovalent: protons research abstracts see: inorganic chemicals: electrolytes: ions: cations: cations, monovalent: protons research

    PUBMED ID PMID:

    MEDLINE DATE:

    Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 104

    Page Numbers: 12761-6

    Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

    ISSN: 0027-8424

    DAY: 24

    MONTH: 07

    YEAR: 2007

    Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7505876

    Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Keywords Mesh Terms:

    KEYWORDS: Protons

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Identification of a chloride ion binding site in Na+/Cl -dependent transporters. Information

    Substance Name: cif nucleoside transporter

    Registry Number: 0

    Grant and Affiliation Information for Identification of a chloride ion binding site in Na+/Cl -dependent transporters.

    AFFILIATION: Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, and Department of Biochemistry and Molecular Biophysics, Columbia University, 1130 St. Nicholas Avenue, Room 815, New York, NY 10032, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDA

    GRANT: DA 007295

    ACRONYM: DA

    MEDLINETA: Proc Natl Acad Sci U S A

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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