3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Yanhe Zhao, Huafeng Wang, Caroline Wiesehoefer, Naman B. Shah, Evan Reetz, Jae Yeon Hwang, Xiaofang Huang, Tse‐En Wang, Polina V. Lishko, Karen M. Davies, Gunther Wennemuth, Daniela Nicastro, Jean‐Ju Chung
Abstract
Abstract The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca 2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9 −/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.