tailieunhanh - Báo cáo y học: " Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity | Li et al. Journal of Biomedical Science 2010 17 89 http content 17 1 89 NSC The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Conserved charged amino acid residues in the extracellular region of sodium iodide symporter are critical for iodide transport activity Chia-Cheng Li1t Tin-Yun Ho1t Chia-Hung Kao2 Shih-Lu Wu3 Ji-An Liang4 Chien-Yun Hsiang5 Abstract Background Sodium iodide symporter NIS mediates the active transport and accumulation of iodide from the blood into the thyroid gland. His-226 located in the extracellular region of NIS has been demonstrated to be critical for iodide transport in our previous study. The conserved charged amino acid residues in the extracellular region of NIS were therefore characterized in this study. Methods Fourteen charged residues Arg-9 Glu-79 Arg-82 Lys-86 Asp-163 His-226 Arg-228 Asp-233 Asp-237 Arg-239 Arg-241 Asp-311 Asp-322 and Asp-331 were replaced by alanine. Iodide uptake abilities of mutants were evaluated by steady-state and kinetic analysis. The three-dimensional comparative protein structure of NIS was further modeled using sodium glucose transporter as the reference protein. Results All the NIS mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However these mutants except R9A displayed severe defects on the iodide uptake. Further kinetic analysis revealed that mutations at conserved positively charged amino acid residues in the extracellular region of NIS led to decrease NIS-mediated iodide uptake activity by reducing the maximal rate of iodide transport while mutations at conserved negatively charged residues led to decrease iodide transport by increasing dissociation between NIS mutants and iodide. Conclusions This is the first report characterizing thoroughly the functional significance of conserved charged amino acid residues in the extracellular