[https://www.uniprot.org/uniprot/SL9C1_STRPU SL9C1_STRPU] Electroneutral sodium:proton antiporter that regulates intracellular pH of sperm along with capacitation and fertility. Activated in response to egg-derived chemoattractants, couples membrane voltage to sodium:proton exchange and transduces membrane hyperpolarization to cytoplasmic alkalization to cAMP signaling and ultimately to sperm motility.<ref>PMID:30022052</ref> <ref>PMID:37880360</ref> <ref>PMID:37880361</ref>
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== Publication Abstract from PubMed ==
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The newly characterized sperm-specific Na(+)/H(+) exchanger stands out by its unique tripartite domain composition(1,2). It unites a classical solute carrier unit with regulatory domains usually found in ion channels, namely, a voltage-sensing domain and a cyclic-nucleotide binding domain(1,3), which makes it a mechanistic chimera and a secondary-active transporter activated strictly by membrane voltage. Our structures of the sea urchin SpSLC9C1 in the absence and presence of ligands reveal the overall domain arrangement and new structural coupling elements. They allow us to propose a gating model, where movements in the voltage sensor indirectly cause the release of the exchanging unit from a locked state through long-distance allosteric effects transmitted by the newly characterized coupling helices. We further propose that modulation by its ligand cyclic AMP occurs by means of disruption of the cytosolic dimer interface, which lowers the energy barrier for S4 movements in the voltage-sensing domain. As SLC9C1 members have been shown to be essential for male fertility, including in mammals(2,4,5), our structure represents a potential new platform for the development of new on-demand contraceptives.
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Structures of a sperm-specific solute carrier gated by voltage and cAMP.,Kalienkova V, Peter MF, Rheinberger J, Paulino C Nature. 2023 Nov;623(7985):202-209. doi: 10.1038/s41586-023-06629-w. Epub 2023 , Oct 25. PMID:37880361<ref>PMID:37880361</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
8pd3 is a 1 chain structure with sequence from Strongylocentrotus purpuratus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
SL9C1_STRPU Electroneutral sodium:proton antiporter that regulates intracellular pH of sperm along with capacitation and fertility. Activated in response to egg-derived chemoattractants, couples membrane voltage to sodium:proton exchange and transduces membrane hyperpolarization to cytoplasmic alkalization to cAMP signaling and ultimately to sperm motility.[1][2][3]
References
↑ Windler F, Bönigk W, Körschen HG, Grahn E, Strünker T, Seifert R, Kaupp UB. The solute carrier SLC9C1 is a Na(+)/H(+)-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding. Nat Commun. 2018 Jul 18;9(1):2809. PMID:30022052 doi:10.1038/s41467-018-05253-x
↑ Yeo H, Mehta V, Gulati A, Drew D. Structure and electromechanical coupling of a voltage-gated Na(+)/H(+) exchanger. Nature. 2023 Nov;623(7985):193-201. PMID:37880360 doi:10.1038/s41586-023-06518-2
↑ Kalienkova V, Peter MF, Rheinberger J, Paulino C. Structures of a sperm-specific solute carrier gated by voltage and cAMP. Nature. 2023 Nov;623(7985):202-209. PMID:37880361 doi:10.1038/s41586-023-06629-w
