- EMDB-64679: Cryo-EM structure of the 48-nm repeat doublet microtubule from mo... -
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Basic information
Entry
Database: EMDB / ID: EMD-64679
Title
Cryo-EM structure of the 48-nm repeat doublet microtubule from mouse sperm
Map data
Sample
Complex: doublet microtubule of mouse sperm flagella
Protein or peptide: x 60 types
Ligand: x 4 types
Keywords
sperm flagellar doublet microtubules / STRUCTURAL PROTEIN
Function / homology
Function and homology information
male germ-line stem cell population maintenance / protein localization to motile cilium / epithelial cilium movement involved in determination of left/right asymmetry / left/right pattern formation / outer acrosomal membrane / regulation of brood size / establishment of left/right asymmetry / 9+0 motile cilium / axonemal microtubule doublet inner sheath / sperm flagellum assembly ...male germ-line stem cell population maintenance / protein localization to motile cilium / epithelial cilium movement involved in determination of left/right asymmetry / left/right pattern formation / outer acrosomal membrane / regulation of brood size / establishment of left/right asymmetry / 9+0 motile cilium / axonemal microtubule doublet inner sheath / sperm flagellum assembly / manchette assembly / axonemal B tubule inner sheath / axonemal A tubule inner sheath / outer dense fiber / sperm axoneme assembly / protein polyglutamylation / positive regulation of feeding behavior / cerebral cortex cell migration / regulation of calcineurin-NFAT signaling cascade / regulation of microtubule nucleation / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Cargo trafficking to the periciliary membrane / Sealing of the nuclear envelope (NE) by ESCRT-III / cerebrospinal fluid circulation / inner dynein arm assembly / epithelial cilium movement involved in extracellular fluid movement / Carboxyterminal post-translational modifications of tubulin / Intraflagellar transport / MAP kinase tyrosine/serine/threonine phosphatase activity / cilium-dependent cell motility / regulation of cilium beat frequency involved in ciliary motility / COPI-independent Golgi-to-ER retrograde traffic / 9+2 motile cilium / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / left/right axis specification / regulation of store-operated calcium entry / intraciliary transport / cilium movement involved in cell motility / COPI-mediated anterograde transport / acrosomal membrane / axoneme assembly / microtubule sliding / Kinesins / cilium movement / sperm DNA condensation / perinuclear theca / PKR-mediated signaling / Aggrephagy / RHO GTPases activate IQGAPs / motile cilium assembly / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / COPI-dependent Golgi-to-ER retrograde traffic / Resolution of Sister Chromatid Cohesion / calcium ion sensor activity / The role of GTSE1 in G2/M progression after G2 checkpoint / Recycling pathway of L1 / cilium organization / axonemal microtubule / cellular response to UV-C / gamma-tubulin ring complex / Hedgehog 'off' state / RHO GTPases Activate Formins / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / cellular response to leukemia inhibitory factor / Separation of Sister Chromatids / Anchoring of the basal body to the plasma membrane / Recruitment of NuMA to mitotic centrosomes / AURKA Activation by TPX2 / manchette / positive regulation of cell motility / ciliary transition zone / determination of left/right symmetry / sperm head-tail coupling apparatus / positive regulation of cilium assembly / Regulation of PLK1 Activity at G2/M Transition / MHC class II antigen presentation / 3'-5'-DNA exonuclease activity / UTP biosynthetic process / CTP biosynthetic process / motile cilium / DNA catabolic process / protein targeting to membrane / nucleoside diphosphate kinase activity / extrinsic component of membrane / : / single fertilization / mRNA stabilization / sperm principal piece / GTP biosynthetic process / intermediate filament / Hydrolases; Acting on ester bonds; Exodeoxyribonucleases producing 5'-phosphomonoesters / spermatid development / AMP binding / centriolar satellite / tubulin complex / protein-serine/threonine phosphatase / intercellular bridge Similarity search - Function
Spermatogenesis-associated protein 48 / Protein of unknown function DUF4555 / Spermatogenesis-associated protein 48 / Sperm-associated microtubule inner protein 4 / Uncharacterized protein C1orf100 / : / Family of unknown function (DUF5530) / Uncharacterised protein family C20orf85 / Protein of unknown function DUF4562 / Spermatid-specific manchette-related protein 1 ...Spermatogenesis-associated protein 48 / Protein of unknown function DUF4555 / Spermatogenesis-associated protein 48 / Sperm-associated microtubule inner protein 4 / Uncharacterized protein C1orf100 / : / Family of unknown function (DUF5530) / Uncharacterised protein family C20orf85 / Protein of unknown function DUF4562 / Spermatid-specific manchette-related protein 1 / Testis-expressed protein 33 / Testis-expressed sequence 37 protein / CFAP97 domain-containing protein 1/2 / Testis-specific serine/threonine-protein kinase 6, catalytic domain / C10orf82-like / : / : / Normal lung function maintenance, Low in Lung Cancer 1 protein / Domain of unknown function (DUF4562) / Spermatid-specific manchette-related protein 1 / TSC21 family / Testis-expressed sequence 33 protein family / Sperm-associated microtubule inner protein 5 / Ciliary microtubule inner protein 3 / Protein phosphatase 1 regulatory subunit 32 / Testis, prostate and placenta-expressed protein / Testis-expressed protein 49 / Protein phosphatase 1 regulatory subunit 32 / Sperm microtubule inner protein 8 / Sperm microtubule inner protein 11 / : / : / Sperm microtubule inner protein 1 / Protein of unknown function DUF1143 / Atypical dual specificity phosphatase, subfamily B / Protein of unknown function DUF4513 / Cilia- and flagella-associated protein 68 / Sperm-associated microtubule inner protein 10 / Protein of unknown function DUF4541 / Tektin bundle interacting protein 1 / Hemingway/CFA97 / Coiled-coil domain-containing protein 105 / : / Hemingway/CFA97 / Tektin bundle interacting protein 1 / Cilia and flagella associated protein 90 / : / FAM183 family / FAM183A and FAM183B related / Sperm-tail PG-rich repeat / Sperm-associated antigen 8 / Cilia- and flagella-associated protein 95 / NDPK7, first NDPk domain / Cilia- and flagella-associated protein 107 / : / Sperm-tail PG-rich repeat / Protein CFAP95 / Cilia- and flagella-associated protein 143 / Cilia and flagella associated protein 107 / Tektin / Cilia- and flagella-associated protein 276 / : / Tektin family / Protein of unknown function (DUF3695) / DJBP, EF-hand domain / EF-hand domain / Uncharacterised protein FAM166/UPF0605 / Cilia- and flagella-associated protein 77 / Protein Flattop / Ciliary microtubule inner protein 2B-like / Cilia- and flagella-associated protein 77 / Flattop / Nucleoside diphosphate kinase 7 / Piercer of microtubule wall 1/2 / Piercer of microtubule wall 1/2 / Cilia- and flagella-associated protein 141 / Cilia- and flagella-associated protein 141 / Cilia- and flagella-associated protein 161-like domain / : / : / EFHB C-terminal EF-hand domain / : / : / Nucleoside diphosphate kinase 7 N-terminal PH domain / Meiosis-specific nuclear structural protein 1 / Cilia- and flagella-associated protein 45 / NDPK7, second NDPk domain / Cilia- and flagella- associated protein 210 / CFAP53/TCHP / Trichohyalin-plectin-homology domain / Trichohyalin-plectin-homology domain / RIB43A / RIB43A / DM10 domain / EF-hand domain-containing protein EFHC1/EFHC2/EFHB / DM10 domain / DM10 domain profile. / Domains in hypothetical proteins in Drosophila, C. elegans and mammals. Occurs singly in some nucleoside diphosphate kinases. / Enkurin domain / : Similarity search - Domain/homology
Cilia- and flagella-associated protein 77 / Luteinizing hormone beta / Cilia- and flagella- associated protein 210 / Tektin bundle-interacting protein 1 / Protein SPMIP1 / Sperm microtubule inner protein 2 / Tektin-5 / Tubulin alpha-3 chain / Tubulin beta-4B chain / Stabilizer of axonemal microtubules 4 ...Cilia- and flagella-associated protein 77 / Luteinizing hormone beta / Cilia- and flagella- associated protein 210 / Tektin bundle-interacting protein 1 / Protein SPMIP1 / Sperm microtubule inner protein 2 / Tektin-5 / Tubulin alpha-3 chain / Tubulin beta-4B chain / Stabilizer of axonemal microtubules 4 / Tektin-4 / Sperm microtubule inner protein 6 / Sperm-associated antigen 8 / Cilia- and flagella-associated protein 107 / Piercer of microtubule wall 1 protein / Cilia- and flagella-associated protein 52 / Cilia- and flagella-associated protein 144 / Protein SPMIP7 / Meiosis-specific nuclear structural protein 1 / Sperm microtubule inner protein 8 / EF-hand calcium-binding domain-containing protein 6 / Protein Flattop / Cilia- and flagella-associated protein 161 / Enkurin / Tektin-3 / EF-hand calcium-binding domain-containing protein 3 / Cilia- and flagella-associated protein 20 / Sperm microtubule inner protein 11 / EF-hand domain-containing family member B / Ciliary microtubule inner protein 3 / Ciliary microtubule associated protein 1A / Tektin-2 / Testis-specific serine/threonine-protein kinase 6 / Cilia- and flagella-associated protein 95 / Sperm-associated microtubule inner protein 5 / RIB43A-like with coiled-coils protein 1 / Cilia- and flagella-associated protein 68 / Cilia- and flagella-associated protein 53 / EF-hand domain-containing family member C2 / Ciliary microtubule inner protein 2A / Tektin-like protein 1 / RIB43A-like with coiled-coils protein 2 / Sperm-associated microtubule inner protein 4 / Dual specificity phosphatase 21 / Cilia- and flagella-associated protein 141 / Sperm-associated microtubule inner protein 10 / Ciliary microtubule inner protein 4 / EF-hand domain-containing protein 1 / Cilia- and flagella-associated protein 45 / Ciliary microtubule inner protein 1 / Protein SPMIP3 / Cilia- and flagella-associated protein 276 / Protein SPMIP9 / Tektin-1 / Parkin coregulated gene protein homolog / Sperm axonemal maintenance protein CFAP97D1 / Cilia- and flagella-associated protein 90 / Ciliary microtubule inner protein 2C / Nucleoside diphosphate kinase 7 / Piercer of microtubule wall 2 protein Similarity search - Component
Biological species
Mus musculus (house mouse)
Method
single particle reconstruction / cryo EM / Resolution: 3.7 Å
National Natural Science Foundation of China (NSFC)
China
Citation
Journal: Nat Commun / Year: 2026 Title: Doublet microtubule-associated tektins and enzymes differentially regulate sperm flagellar integrity and motility. Authors: Qi Liu / Lunni Zhou / Xiaochen Liang / Pengyu Chen / Bo Li / Shuo Yang / Yuqi Liu / Haibo Zhao / Jin Hu / Shan Feng / Shanshan Xie / Jianping Wu / Miao Gui / Abstract: Doublet microtubule (DMT)-associated proteins assemble and drive sperm flagella, which are essential for successful fertilization. However, the exact roles of different DMT-associated proteins in ...Doublet microtubule (DMT)-associated proteins assemble and drive sperm flagella, which are essential for successful fertilization. However, the exact roles of different DMT-associated proteins in sperm function and the underlying molecular mechanisms remain elusive. Here, we generate four gene-knockout mice based on high-resolution structures targeting distinct DMT components: two intermediate filament-like tektins (TEKT1, TEKT5) and two enzymes (TSSK6, DUSP21). The depletion of TEKT1, shared by sperm flagella and motile cilia, causes male infertility characterized by impaired sperm motility and loss of the tektin bundle, whereas sperm-specific Tekt5 knockout (KO) mice remain fertile with largely normal flagellar function, indicating functional divergence within the tektin family. Tssk6 KO spermatozoa exhibit severely disturbed morphology and motility, resulting in homozygote infertility and heterozygote subfertility. Phosphoproteomics reveals dysregulated phosphorylation of axonemal proteins, highlighting the critical role of kinase-mediated signaling in regulating sperm motility. Conversely, Dusp21 KO mice display no fertility or sperm motility defects, suggesting compensatory phosphatase activity. Phenotypic comparisons between Tekt1 and Tssk6 KO mice suggest their involvement in distinct subtypes of asthenozoospermia. Overall, this study elucidates how filamentous and enzymatic DMT proteins govern sperm function through divergent mechanisms, which have implications for molecular diagnosis of male infertility.
Name: Tubulin alpha-3 chain / type: protein_or_peptide / ID: 8 / Number of copies: 167 / Enantiomer: LEVO EC number: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
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