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-Structure paper
Title | Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility. |
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Journal, issue, pages | Cell, Vol. 186, Issue 13, Page 2897-2910.e19, Year 2023 |
Publish date | Jun 22, 2023 |
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 / |
PubMed 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. |
External links | Cell / PubMed:37295417 |
Methods | EM (single particle) |
Resolution | 3.07 - 4.34 Å |
Structure data | EMDB-35810: Cryo-EM structure of the 48-nm repeat doublet microtubule from human sperm EMDB-35823, PDB-8iyj: EMDB-36458: Local map of the mouse sperm doublet microtubule (Middel01) EMDB-36498: Overall consensus map of the mouse sperm doublet microtubule EMDB-36499: Local map of the mouse sperm doublet microtubule (Lower01) EMDB-36500: Local map of the mouse sperm doublet microtubule (Upper10) EMDB-36501: Local map of the mouse sperm doublet microtubule (Middle02) EMDB-36502: Local map of the mouse sperm doublet microtubule (Lower02) EMDB-36503: Local map of the mouse sperm doublet microtubule (Upper09) EMDB-36504: Local map of the mouse sperm doublet microtubule (Middle03) EMDB-36509: Local map of the mouse sperm doublet microtubule (Lower03) EMDB-36510: Local map of the mouse sperm doublet microtubule (Middle04) EMDB-36511: Local map of the mouse sperm doublet microtubule (Upper08) EMDB-36513: Local map of the mouse sperm doublet microtubule (Lower04) EMDB-36514: Local map of the mouse sperm doublet microtubule (Upper07) EMDB-36515: Local map of the mouse sperm doublet microtubule (Middle05) EMDB-36516: Local map of the mouse sperm doublet microtubule (Lower05) EMDB-36517: Local map of the mouse sperm doublet microtubule (Upper06) EMDB-36518: Local map of the mouse sperm doublet microtubule (Middle06) EMDB-36519: Local map of the mouse sperm doublet microtubule (Lower06) EMDB-36520: Local map of the mouse sperm doublet microtubule (Upper05) EMDB-36521: Local map of the mouse sperm doublet microtubule (Middle07) EMDB-36523: Local map of the mouse sperm doublet microtubule (Upper04) EMDB-36524: Local map of the mouse sperm doublet microtubule (Middle08) EMDB-36525: Local map of the mouse sperm doublet microtubule (Lower07) EMDB-36526: Local map of the mouse sperm doublet microtubule (Upper03) EMDB-36527: Local map of the mouse sperm doublet microtubule (Middle09) EMDB-36528: Local map of the mouse sperm doublet microtubule (Lower08) EMDB-36529: Local map of the mouse sperm doublet microtubule (Upper02) EMDB-36530: Local map of the mouse sperm doublet microtubule (Middle10) EMDB-36531: Local map of the mouse sperm doublet microtubule (Lower09) EMDB-36532: Local map of the mouse sperm doublet microtubule (Upper01) EMDB-36533: Local map of the mouse sperm doublet microtubule (Lower10) EMDB-36534: Overall consensus map of the human sperm doublet microtubule EMDB-36536: Local map of the human sperm doublet microtubule (Lower01) EMDB-36537: Local map of the human sperm doublet microtubule (Lower02) EMDB-36538: Local map of the human sperm doublet microtubule (Lower03) EMDB-36539: Local map of the human sperm doublet microtubule (Lower04) EMDB-36540: Local map of the human sperm doublet microtubule (Lower05) EMDB-36542: Local map of the human sperm doublet microtubule (Lower06) EMDB-36543: Local map of the human sperm doublet microtubule (Lower07) EMDB-36544: Local map of the human sperm doublet microtubule (Lower08) EMDB-36545: Local map of the human sperm doublet microtubule (Lower09) EMDB-36546: Local map of the human sperm doublet microtubule (Lower10) EMDB-36547: Local map of the human sperm doublet microtubule (Middle01) EMDB-36549: Local map of the human sperm doublet microtubule (Middle02) EMDB-36550: Local map of the human sperm doublet microtubule (Middle03) EMDB-36551: Local map of the human sperm doublet microtubule (Middle04) EMDB-36552: Local map of the human sperm doublet microtubule (Middle05) EMDB-36553: Local map of the human sperm doublet microtubule (Middle06) EMDB-36554: Local map of the human sperm doublet microtubule (Middle07) EMDB-36555: Local map of the human sperm doublet microtubule (Middle08) EMDB-36556: Local map of the human sperm doublet microtubule (Middle09) EMDB-36557: Local map of the human sperm doublet microtubule (Middle10) EMDB-36558: Local map of the human sperm doublet microtubule (Upper01) EMDB-36559: Local map of the human sperm doublet microtubule (Upper02) EMDB-36560: Local map of the human sperm doublet microtubule (Upper03) EMDB-36561: Local map of the human sperm doublet microtubule (Upper04) EMDB-36562: Local map of the human sperm doublet microtubule (Upper05) EMDB-36564: Local map of the human sperm doublet microtubule (Upper06) EMDB-36565: Local map of the human sperm doublet microtubule (Upper07) EMDB-36566: Local map of the human sperm doublet microtubule (Upper08) EMDB-36567: Local map of the human sperm doublet microtubule (Upper09) EMDB-36568: Local map of the human sperm doublet microtubule (Upper10) EMDB-36580: Local map of the mouse sperm doublet microtubule (Upper_ODF3A) EMDB-36581: Local map of the mouse sperm doublet microtubule (Middle_ODF3A) EMDB-36582: Local map of the mouse sperm doublet microtubule (Lower_ODF3A) EMDB-36583: Local map of the mouse sperm doublet microtubule (Middle_A13) EMDB-36584: Local map of the mouse sperm doublet microtubule (Upper_A13) EMDB-36585: Local map of the mouse sperm doublet microtubule (TSSK6) EMDB-36586: Local map of the mouse sperm doublet microtubule (A07_A08) EMDB-36587: Local map of the mouse sperm doublet microtubule (DUSP21_TEX37) EMDB-36588: Local map of the mouse sperm doublet microtubule (A09_A10) EMDB-36591: Local map of the mouse sperm doublet microtubule (A13_A01_A02) |
Chemicals | ChemComp-GTP: ChemComp-MG: ChemComp-GDP: |
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Keywords | STRUCTURAL PROTEIN / doublet microtubule |