@article{69a4720e80774bfa851cf2e21fe4fd76,
title = "3D structure and in situ arrangements of CatSper channel in the sperm flagellum",
abstract = "The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ 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.",
author = "Yanhe Zhao and Huafeng Wang and Caroline Wiesehoefer and Shah, {Naman B.} and Evan Reetz and Hwang, {Jae Yeon} and Xiaofang Huang and Wang, {Tse en} and Lishko, {Polina V.} and Davies, {Karen M.} and Gunther Wennemuth and Daniela Nicastro and Chung, {Jean Ju}",
note = "Funding Information: Authors thank Drs. Jun Liu and Shiwei Zhu for help in initial trials of mouse sperm cryo-ET at the Yale West campus Cryo-EM core, Dr. Daniel Stoddard for providing EM training and management of the UT Southwestern Medical Center (UTSW) cryo-electron microscope facility (funded in part by a Cancer Prevention and Research Institute of Texas Core Facility Award (RP170644)), David Mastronarde and John Heumann (University of Colorado at Boulder) for continued development of image processing tools, J{\"u}rgen Heger for the trajectory videos, the BioHPC supercomputing facility located in the Lyda Hill Department of Bioinformatics at UTSW for the computational resources and Dr. Fred Sigworth for critically reading of the initial draft. This work was funded by the National Institutes of Health (R01HD096745 to J.-J.C., R01GM083122 to D.N., R01GM111802 to P.V.L.), the Cancer Prevention and Research Institute of Texas (RR140082 to D.N.), the Grantham Foundation to J.-J.C. the Pew Biomedical Scholars Award and Rose Hill award to P.V.L., in part by the Office of Science of the US Department of Energy (DE-AC02-O5CH11231) and UCB start-up funds to K.M.D., and the Deutsche Forschungsgemeinschaft (2344/9-3 to G.W.). J.Y.H. and X.H. are recipients of the Male Contraceptive Initiative and James Hudson Brown-Alexander B. Coxe Postdoctoral Fellowship, respectively. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-31050-8",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}