Human aquaporin-1 (hAQP1) is a channel protein which selectively facilitates translocation of water across the cell membrane, serving important physiological functions including epithelial fluid transport in the renal system. Several crystal structures of hAQP1 have been determined at moderate resolution, but these structures broadly diverge in their representation of hAQP1’s long extracellular loop C, which may participate in functionally relevant interactions with the residues defining the protein’s central pore. This work investigates the structure of loop C at non-cryogenic temperature in a native-like lipid environment via MAS SSNMR spectroscopy. Selective recoupling through homogeneously broadened rotational resonance was applied in multidimensional correlation experiments in order to observe internuclear correlations involving loop C residues. The observed correlations provided sufficient distance restraints to develop a refined structural model of loop C using the molecular structure determination program Xplor-NIH. The refined model accounts for physiologically relevant interactions between the loop and the central pore.
- Dr. Hermann Eberl, Chair
- Dr. Vladimir Ladizhansky, Advisor
- Dr. Leonid Brown, Co-Advisor
- Dr. George Harauz, Graduate Faculty