Bridging The Gap Between Functional And Structural Data

BIOPHYSICAL JOURNAL(2019)

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摘要
The voltage at the outer and inner membrane-solution interface deviates from the voltage at the bulk solution. This is due to fixed charges at the membrane surface. Charged residues of proteins that are exposed to the aqueous solution contribute to these charges. The voltage that drops across the membrane is therefore set by the difference of the inner and outer membrane surface potential and not by the bulk potential. By utilizing capacitance measurements, we have recently shown that ligand binding to membrane proteins changes the surface potential and that this is seen by a change in apparent capacitance. It is conceivable that also rearrangement of solvent-accessible charged residues, as can occur in conformational transitions, change the surface potential. We tested this hypothesis by incorporating structural information of the serotonin transporter (SERT) into a kinetic model of the transport cycle. For this, we counted the number of water-accessible charges of SERT for different conformational states. Using a kinetic model, we then were able to calculate the time dependent change of the inner and outer net surface charge densities during the transport cycle. Subsequently, this allowed us to determine the associated capacitance changes. Comparison with experimental data revealed that the capacitance signal estimated from structural data is similar in size and shape. Thus, the complex capacitance signal of the SERT transport cycle derives mainly from changes in surface potential due to conformational transitions. We further propose that capacitance measurements in combination with kinetic models might serve as a useful tool to link functional and structural information.
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关键词
structural data,functional
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