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New landmark publication from Paulino group: Structures of a sperm-specific solute carrier gated by voltage and cAMP
Date: October 25, 2023Published: 25 October 2023
The Paulino Group has characterized a sperm-specific Na+/H+ exchanger with a unique tripartite domain composition, combining a solute carrier unit with regulatory domains typically found in ion channels. Our structures of the sea urchin SpSLC9C1 reveal new structural coupling elements and suggest a gating model where voltage sensor movements trigger the release of the exchanger through long-distance allosteric effects. We also propose that cyclic AMP modulates the exchanger by disrupting the dimer interface, lowering the energy barrier for voltage-sensing domain movements. Given the role of SLC9C1 in male fertility, this structure could serve as a platform for developing new on-demand contraceptives.
Publication: Kalienkova, V., Peter, M.F., Rheinberger, J. et al. Structures of a sperm-specific solute carrier gated by voltage and cAMP. Nature 623, 202–209 (2023). https://doi.org/10.1038/s41586-023-06629-w [Abstract]
The Paulino Group has characterized a sperm-specific Na+/H+ exchanger with a unique tripartite domain composition, combining a solute carrier unit with regulatory domains typically found in ion channels. Our structures of the sea urchin SpSLC9C1 reveal new structural coupling elements and suggest a gating model where voltage sensor movements trigger the release of the exchanger through long-distance allosteric effects. We also propose that cyclic AMP modulates the exchanger by disrupting the dimer interface, lowering the energy barrier for voltage-sensing domain movements. Given the role of SLC9C1 in male fertility, this structure could serve as a platform for developing new on-demand contraceptives.
Publication: Kalienkova, V., Peter, M.F., Rheinberger, J. et al. Structures of a sperm-specific solute carrier gated by voltage and cAMP. Nature 623, 202–209 (2023). https://doi.org/10.1038/s41586-023-06629-w [Abstract]
