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Publication : Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility.

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.
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