National Natural Science Foundation of China (NSFC)
32271261
China
Citation
Journal: Cell / Year: 2023 Title: Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility. Authors: Lunni Zhou / Haobin Liu / Siyu Liu / Xiaoyu Yang / Yue Dong / Yun Pan / Zhuang Xiao / Beihong Zheng / Yan Sun / Pengyu Huang / Xixi Zhang / Jin Hu / Rui Sun / Shan Feng / Yi Zhu / Mingxi Liu ...Authors: Lunni Zhou / Haobin Liu / Siyu Liu / Xiaoyu Yang / Yue Dong / Yun Pan / Zhuang Xiao / Beihong Zheng / Yan Sun / Pengyu Huang / Xixi Zhang / Jin Hu / Rui Sun / Shan Feng / Yi Zhu / Mingxi Liu / Miao Gui / Jianping Wu / Abstract: Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron ...Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.
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