8PDU

cGMP-bound SpSLC9C1 in lipid nanodiscs, dimer

8PDU の概要

• エントリーDOI: 10.2210/pdb8pdu/pdb
• EMDBエントリー: 17621
• 分子名称: Sperm-specific sodium proton exchanger, CYCLIC GUANOSINE MONOPHOSPHATE (2 entities in total)
• 機能のキーワード: slc9, nhe, sperm-specific, membrane protein
• 由来する生物種: Strongylocentrotus purpuratus (purple sea urchin)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 295939.38

構造登録者

Kalienkova, V.,Peter, M.,Rheinberger, J.,Paulino, C. (登録日: 2023-06-12, 公開日: 2023-11-08, 最終更新日: 2023-11-15)

主引用文献

Kalienkova, V.,Peter, M.F.,Rheinberger, J.,Paulino, C.
Structures of a sperm-specific solute carrier gated by voltage and cAMP.
Nature, 623:202-209, 2023

PubMed Abstract: The newly characterized sperm-specific Na/H exchanger stands out by its unique tripartite domain composition. 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, 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, our structure represents a potential new platform for the development of new on-demand contraceptives.

PubMed: 37880361
DOI: 10.1038/s41586-023-06629-w

実験手法

ELECTRON MICROSCOPY (3.22 Å)