First Author | Zhou L | Year | 2023 |
Journal | Cell | Volume | 186 |
Issue | 13 | Pages | 2897-2910.e19 |
PubMed ID | 37295417 | Mgi Jnum | J:338030 |
Mgi Id | MGI:7495398 | Doi | 10.1016/j.cell.2023.05.009 |
Citation | Zhou L, et al. (2023) Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility. Cell 186(13):2897-2910.e19 |
abstractText | 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. |