The SLC4 family of secondary bicarbonate transporters is responsible for the transport of HCO, CO, Cl, Na, K, NH, and H, which are necessary for regulation of pH and ion homeostasis. They are widely expressed in numerous tissues throughout the body and function in different cell types with different membrane properties. Potential lipid roles in SLC4 function have been reported in experimental studies, focusing mostly on two members of the family: AE1 (Cl/HCO exchanger) and NBCe1 (Na-COcotransporter).
View Article and Find Full Text PDFUnlabelled: The SLC4 family of secondary bicarbonate transporters is responsible for the transport of HCO -, CO , Cl , Na , K , NH and H necessary for regulation of pH and ion homeostasis. They are widely expressed in numerous tissues throughout the body and function in different cell types with different membrane properties. Potential lipid roles in SLC4 function have been reported in experimental studies, focusing mostly on two members of the family: AE1 (Cl /HCO exchanger) and NBCe1 (Na -CO cotransporter).
View Article and Find Full Text PDFAnion exchanger 1 (AE1, band 3) is a major membrane protein of red blood cells and plays a key role in acid-base homeostasis, urine acidification, red blood cell shape regulation, and removal of carbon dioxide during respiration. Though structures of the transmembrane domain (TMD) of three SLC4 transporters, including AE1, have been resolved previously in their outward-facing (OF) state, no mammalian SLC4 structure has been reported in the inward-facing (IF) conformation. Here we present the cryoEM structures of full-length bovine AE1 with its TMD captured in both IF and OF conformations.
View Article and Find Full Text PDFSLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown.
View Article and Find Full Text PDFThe human sodium iodide symporter (hNIS) is a theranostic reporter gene which concentrates several clinically approved SPECT and PET radiotracers and plays an essential role for the synthesis of thyroid hormones as an iodide transporter in the thyroid gland. Development of hNIS mutants which could enhance translocation of the desired imaging ions is currently underway. Unfortunately, it is hindered by lack of understanding of the 3D organization of hNIS and its relation to anion transport.
View Article and Find Full Text PDFThe sodium iodide symporter (NIS) transports iodide, which is necessary for thyroid hormone production. NIS also transports other monovalent anions such as tetrafluoroborate (BF4-), pertechnetate (TcO4-), and thiocyanate (SCN-), and is competitively inhibited by perchlorate (ClO4-). However, the mechanisms of substrate selectivity and inhibitor sensitivity are poorly understood.
View Article and Find Full Text PDFFluorescent dyes revolutionized and expanded our understanding of biological membranes. The interpretation of experimental fluorescence data in terms of membrane structure, however, requires detailed information about the molecular environment of the dyes. Nile red is a fluorescent molecule whose excitation and emission maxima depend on the polarity of the solvent.
View Article and Find Full Text PDFThe performance of the second-order spin-flip constricted variational density functional theory (SF-CV(2)-DFT) for the calculation of the exchange coupling constant (J) is assessed by application to a series of triply bridged Cu(II) dinuclear complexes. A comparison of the J values based on SF-CV(2)-DFT with those obtained by the broken symmetry (BS) DFT method and experiment is provided. It is demonstrated that our methodology constitutes a viable alternative to the BS-DFT method.
View Article and Find Full Text PDFWe have recently developed a methodology for the calculation of exchange coupling constants J in weakly interacting polynuclear metal clusters. The method is based on unrestricted and restricted second order spin-flip constricted variational density functional theory (SF-CV(2)-DFT) and is here applied to eight binuclear copper systems. Comparison of the SF-CV(2)-DFT results with experiment and with results obtained from other DFT and wave function based methods has been made.
View Article and Find Full Text PDFWe present a test of a recently developed density functional theory (DFT) based methodology for the calculation of magnetic circular dichroism (MCD) spectra in the presence of zero-field splitting (ZFS). The absorption and MCD spectra of the trinuclear copper complex μ(3)O ([Cu(3)(L)(μ(3)-O)](4+)), which models the native intermediate produced in the catalytic cycle of the multicopper oxidases, have been simulated from first principle within the framework of adiabatic time dependent density functional theory. The effects of the ZFS of the quartet (4)A(2) ground state on the theoretical MCD spectrum of μ(3)O have been analyzed.
View Article and Find Full Text PDFThe excitation, circular dichroism, magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) spectra of small models of four blue copper proteins are simulated on the TDDFT/BP86 level. X-Ray diffraction geometries are used for the modeling of the blue copper sites in azurin, plastocyanin, cucumber basic protein, and nitrite reductase. Comparison with experimental data reveals that the calculations reproduce most of the qualitative trends of the observed experimental spectra with some discrepancies in the orbital decompositions and the values of the excitation energies, the g( parallel) components of the g tensor, and the components of the A tensor.
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