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Structure paper

タイトルStructural diversity of axonemes across mammalian motile cilia.
ジャーナル・号・ページNature, Vol. 637, Issue 8048, Page 1170-1177, Year 2025
掲載日2025年1月1日
著者Miguel Ricardo Leung / Chen Sun / Jianwei Zeng / Jacob R Anderson / Qingwei Niu / Wei Huang / Willem E M Noteborn / Alan Brown / Tzviya Zeev-Ben-Mordehai / Rui Zhang /
PubMed 要旨Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the ...Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii, structures of mammalian axonemes are incomplete. Furthermore, we do not fully understand how molecular structures of axonemes vary across motile-ciliated cell types in the body. Here we use cryoelectron microscopy, cryoelectron tomography and proteomics to resolve the 96-nm modular repeat of axonemal doublet microtubules (DMTs) from both sperm flagella and epithelial cilia of the oviduct, brain ventricles and respiratory tract. We find that sperm DMTs are the most specialized, with epithelial cilia having only minor differences across tissues. We build a model of the mammalian sperm DMT, defining the positions and interactions of 181 proteins including 34 newly identified proteins. We elucidate the composition of radial spoke 3 and uncover binding sites of kinases associated with regeneration of ATP and regulation of ciliary motility. We discover a sperm-specific, axoneme-tethered T-complex protein ring complex (TRiC) chaperone that may contribute to construction or maintenance of the long flagella of mammalian sperm. We resolve axonemal dyneins in their prestroke states, illuminating conformational changes that occur during ciliary movement. Our results illustrate how elements of chemical and mechanical regulation are embedded within the axoneme, providing valuable resources for understanding the aetiology of ciliopathy and infertility, and exemplifying the discovery power of modern structural biology.
リンクNature / PubMed:39743588 / PubMed Central
手法EM (サブトモグラム平均) / EM (単粒子)
解像度3.4 - 12.96 Å
構造データ

EMDB-45677: 96-nm repeat of axonemal doublet microtubules from porcine oviduct cilia, subtomogram average segment 1 of 4
手法: EM (サブトモグラム平均) / 解像度: 9.6 Å

EMDB-45678: 96-nm repeat of axonemal doublet microtubules from porcine oviduct cilia, subtomogram average segment 2 of 4
手法: EM (サブトモグラム平均) / 解像度: 9.4 Å

EMDB-45679: 96-nm repeat of axonemal doublet microtubules from porcine oviduct cilia, subtomogram average segment 3 of 4
手法: EM (サブトモグラム平均) / 解像度: 9.3 Å

EMDB-45680: 96-nm repeat of axonemal doublet microtubules from porcine oviduct cilia, subtomogram average segment 4 of 4
手法: EM (サブトモグラム平均) / 解像度: 10.0 Å

EMDB-45683: Dynein motor inner dynein arm subform c (IDAc) from bovine Fallopian tube
手法: EM (単粒子) / 解像度: 7.92 Å

EMDB-45684: Dynein motor inner dynein arm subform e (IDAe) from bovine Fallopian tube
手法: EM (単粒子) / 解像度: 8.82 Å

EMDB-45685: Dynein motor inner dynein arm subform f (IDAf) from bovine Fallopian tube
手法: EM (単粒子) / 解像度: 8.79 Å

EMDB-45686: The nexin-dynein regulatory complex (N-DRC) from bovine Fallopian tube, distal part
手法: EM (単粒子) / 解像度: 9.15 Å

EMDB-45687: The nexin-dynein regulatory complex (N-DRC) from bovine Fallopian tube, base part
手法: EM (単粒子) / 解像度: 3.83 Å

EMDB-45688: The Outer Dynein Arm (ODA) complex from bovine Fallopian tube
手法: EM (単粒子) / 解像度: 8.68 Å

EMDB-45689: The Outer Dynein Arm-Docking Complex (ODA-DC) from bovine Fallopian tube
手法: EM (単粒子) / 解像度: 3.64 Å

EMDB-45690: Dyneins in pre-state from bovine Fallopian tube (part 1)
手法: EM (単粒子) / 解像度: 7.8 Å

EMDB-45691: Dyneins in pre-state from bovine Fallopian tube (part 2)
手法: EM (単粒子) / 解像度: 7.57 Å

EMDB-45692: Radial Spoke 1 from bovine Fallopian tube, base and stalk
手法: EM (単粒子) / 解像度: 6.59 Å

EMDB-45693: Radial Spoke 1 from bovine Fallopian tube, stalk and head
手法: EM (単粒子) / 解像度: 8.67 Å

EMDB-45694: Radial Spoke 2 from bovine Fallopian tube, base and stalk
手法: EM (単粒子) / 解像度: 8.06 Å

EMDB-45695: Radial Spoke 2 from bovine Fallopian tube, stalk and head
手法: EM (単粒子) / 解像度: 9.21 Å

EMDB-45696: Radial Spoke 3 from bovine Fallopian tube, base and stalk
手法: EM (単粒子) / 解像度: 5.86 Å

EMDB-45697: Radial Spoke 3 from bovine Fallopian tube, stalk and head
手法: EM (単粒子) / 解像度: 9.95 Å

EMDB-45698: FAP206 from bovine Fallopian tube
手法: EM (単粒子) / 解像度: 3.4 Å

EMDB-45699: Dynein motor inner dynein arm subform c (IDAc) from Porcine brain ventricles
手法: EM (単粒子) / 解像度: 7.8 Å

EMDB-45713: Radial Spoke 3 from Pocine brain ventricles, stalk and head
手法: EM (単粒子) / 解像度: 9.72 Å

EMDB-45714: The nexin-dynein regulatory complex (N-DRC) from human fallopian tube, distal part
手法: EM (単粒子) / 解像度: 6.77 Å

EMDB-45715: The nexin-dynein regulatory complex (N-DRC) from human fallopian tube, base part
手法: EM (単粒子) / 解像度: 3.95 Å

EMDB-45716: The Outer Dynein Arm (ODA) complex from human fallopian tube
手法: EM (単粒子) / 解像度: 7.8 Å

EMDB-45717: The Outer Dynein Arm-Docking Complex (ODA-DC) from human fallopian tube
手法: EM (単粒子) / 解像度: 3.47 Å

EMDB-45718: Dyneins in pre-state from human fallopian tube (part 1)
手法: EM (単粒子) / 解像度: 6.89 Å

EMDB-45719: Dyneins in pre-state from human fallopian tube (part 2)
手法: EM (単粒子) / 解像度: 7.79 Å

EMDB-45720: Radial Spoke 1 from human fallopian tube, base and stalk
手法: EM (単粒子) / 解像度: 6.74 Å

EMDB-45721: Radial Spoke 1 from human fallopian tube, stalk and head
手法: EM (単粒子) / 解像度: 10.55 Å

EMDB-45722: Radial Spoke 2 from human fallopian tube, base and stalk
手法: EM (単粒子) / 解像度: 7.54 Å

EMDB-45723: Radial Spoke 2 from human fallopian tube, stalk and head
手法: EM (単粒子) / 解像度: 12.96 Å

EMDB-45724: Radial Spoke 3 from human fallopian tube, base and stalk
手法: EM (単粒子) / 解像度: 6.52 Å

EMDB-45725: Radial Spoke 3 from human fallopian tube, stalk and head
手法: EM (単粒子) / 解像度: 5.83 Å

EMDB-45783: Composite map of bovine Fallopian tube cilia in 96nm repeat
手法: EM (単粒子) / 解像度: 3.52 Å

EMDB-45784: Composite map of porcine brain ventricle cilia in 96nm repeat
手法: EM (単粒子) / 解像度: 3.65 Å

EMDB-45785: Composite map of human Fallopian tube cilia in 96nm repeat
手法: EM (単粒子) / 解像度: 3.56 Å

EMDB-45790: Dynein motor inner dynein arm subform f (IDAf) from human fallopian tube
手法: EM (単粒子) / 解像度: 9.26 Å

EMDB-45801: Cryo-EM structure of bovine Fallopian tube cilia doublet microtubule (48-nm periodicity)
PDB-9cpb: Atomic model of bovine Fallopian tube cilia doublet microtubule (48-nm periodicity)
手法: EM (単粒子) / 解像度: 3.52 Å

EMDB-45802: Cryo-EM structure of porcine brain ventricles cilia doublet microtubule (48-nm periodicity)
PDB-9cpc: Atomic model of porcine brain ventricles cilia doublet microtubule (48-nm periodicity)
手法: EM (単粒子) / 解像度: 3.65 Å

EMDB-50866: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS1 base local refinement
手法: EM (単粒子) / 解像度: 3.9 Å

EMDB-50867: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS1 stalk local refinement
手法: EM (単粒子) / 解像度: 5.1 Å

EMDB-50868: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS1 head local refinement
手法: EM (単粒子) / 解像度: 3.9 Å

EMDB-50869: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS2 base local refinement
手法: EM (単粒子) / 解像度: 4.1 Å

EMDB-50870: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS2 stalk local refinement
手法: EM (単粒子) / 解像度: 4.5 Å

EMDB-50871: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS2 head local refinement
手法: EM (単粒子) / 解像度: 3.8 Å

EMDB-50872: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS3 base local refinement
手法: EM (単粒子) / 解像度: 4.3 Å

EMDB-50873: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS3 stalk local refinement
手法: EM (単粒子) / 解像度: 4.1 Å

EMDB-50874: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS3 head local refinement
手法: EM (単粒子) / 解像度: 4.6 Å

EMDB-50875: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS1 barrel local refinement
手法: EM (単粒子) / 解像度: 7.4 Å

EMDB-50876: 96-nm repeat of axonemal doublet microtubules from bovine sperm, RS2-RS3 bridge local refinement
手法: EM (単粒子) / 解像度: 7.0 Å

EMDB-50877: 96-nm repeat of axonemal doublet microtubules from bovine sperm, N-DRC baseplate local refinement
手法: EM (単粒子) / 解像度: 3.5 Å

EMDB-50878: 96-nm repeat of axonemal doublet microtubules from bovine sperm, N-DRC distal lobe local refinement
手法: EM (単粒子) / 解像度: 4.7 Å

EMDB-50879: 96-nm repeat of axonemal doublet microtubules from bovine sperm, IDAab local refinement
手法: EM (単粒子) / 解像度: 3.9 Å

EMDB-50880: 96-nm repeat of axonemal doublet microtubules from bovine sperm, IDAc local refinement
手法: EM (単粒子) / 解像度: 4.0 Å

EMDB-50881: 96-nm repeat of axonemal doublet microtubules from bovine sperm, IDAe local refinement
手法: EM (単粒子) / 解像度: 7.2 Å

EMDB-50882: 96-nm repeat of axonemal doublet microtubules from bovine sperm, IDAf IC/LC local refinement
手法: EM (単粒子) / 解像度: 8.2 Å

EMDB-50883: 96-nm repeat of axonemal doublet microtubules from bovine sperm, IDAf motors pre-state local refinement part 1
手法: EM (単粒子) / 解像度: 4.6 Å

EMDB-50884: 96-nm repeat of axonemal doublet microtubules from bovine sperm, IDAf motors pre-state local refinement part 2
手法: EM (単粒子) / 解像度: 5.9 Å

EMDB-50885: 96-nm repeat of axonemal doublet microtubules from bovine sperm, ODA-DC local refinement
手法: EM (単粒子) / 解像度: 4.2 Å

EMDB-50886: 96-nm repeat of axonemal doublet microtubules from bovine sperm, ODA local refinement
手法: EM (単粒子) / 解像度: 7.1 Å

EMDB-50887: 96-nm repeat of axonemal doublet microtubules from bovine sperm, ARMH1 subcomplex local refinement
手法: EM (単粒子) / 解像度: 4.6 Å

EMDB-53135: native axonemal doublet microtubule from bovine sperm, 96-nm repeat (consensus refinement, microtubule-centered)
手法: EM (単粒子) / 解像度: 3.5 Å

PDB-9fqr:
96-nm repeat of axonemal doublet microtubules from bovine sperm
手法: ELECTRON MICROSCOPY / 解像度: 5 Å

化合物

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP / GDP, エネルギー貯蔵分子*YM

ChemComp-MG:
Unknown entry / マグネシウムジカチオン

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子*YM

由来
  • sus scrofa (ブタ)
  • bos taurus (ウシ)
  • Homo sapiens (ヒト)
キーワードSTRUCTURAL PROTEIN / axoneme / cilia / microtubule / dynein / Fallopian tube / doublet microtubule (DMT) / brain ventricle / sperm

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