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Molecular Interactions between a Fluoride Ion Channel and Synthetic Protein Blockers.
Turman, Daniel L; Cheloff, Abraham Z; Corrado, Alexis D; Nathanson, Jacob T; Miller, Christopher.
Afiliación
  • Turman DL; Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
  • Cheloff AZ; Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
  • Corrado AD; Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
  • Nathanson JT; Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
  • Miller C; Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
Biochemistry ; 57(7): 1212-1218, 2018 02 20.
Article en En | MEDLINE | ID: mdl-29393634
Fluoride ion channels of the Fluc family selectively export F- ions to rescue unicellular organisms from acute F- toxicity. Crystal structures of bacterial Fluc channels in complex with synthetic monobodies, fibronectin-derived soluble ß-sandwich fold proteins, show 2-fold symmetric homodimers with an antiparallel transmembrane topology. Monobodies also block Fluc F- current via a pore blocking mechanism. However, little is known about the energetic contributions of individual monobody residues to the affinity of the monobody-channel complex or whether the structural paratope corresponds to functional reality. This study seeks to structurally identify and compare residues interacting with Fluc between two highly similar monobodies and subjects them to mutagenesis and functional measurements of equilibrium affinities via a fluorescence anisotropy binding assay to determine their energetic contributions. The results indicate that the functional and structural paratopes strongly agree and that many Tyr residues at the interface, while playing a key role in affinity, can be substituted with Phe and Trp without large disruptions.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Chaperonas Moleculares / Proteínas de Escherichia coli / Escherichia coli / Fluoruros / Canales Iónicos Idioma: En Revista: Biochemistry Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Chaperonas Moleculares / Proteínas de Escherichia coli / Escherichia coli / Fluoruros / Canales Iónicos Idioma: En Revista: Biochemistry Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos