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-Structure paper
| タイトル | Axonemal dynein contributions to flagellar beat types and waveforms. |
|---|---|
| ジャーナル・号・ページ | bioRxiv, Year 2025 |
| 掲載日 | 2025年11月7日 |
 著者 | Sophia Fochler / Matthew H Doran / Tom Beneke / James Smith / Cecile Fort / Benjamin J Walker / Alan Brown / Eva Gluenz / Richard J Wheeler /    |
| PubMed 要旨 | Eukaryotic flagella, or motile cilia, are iconic molecular machines whose beating drives cell propulsion and fluid transport across diverse organisms. Beat type and waveform are tailored to function, ...Eukaryotic flagella, or motile cilia, are iconic molecular machines whose beating drives cell propulsion and fluid transport across diverse organisms. Beat type and waveform are tailored to function, differing between species and cell types, and individual flagella can switch between beat types. Aberrant beating causes ciliopathies and infertility in humans and prevents unicellular parasite transmission. Eight distinct dynein motor protein complexes bind to axonemal doublet microtubules (DMTs) within flagella and drive beating, yet despite extensive structural analysis, how this machinery achieves different beat types is unknown. Here, using the flagellate unicellular parasite , we show a division of labour where specific dyneins drive specific beat types. Using cryo-EM, we determined the structure of the 96-nm repeat unit of the DMT and identified its dynein composition. We used CRISPR-Cas9 to systematically delete all 96-nm repeat proteins, comprehensively mapping necessity for swimming, and determined the contribution of each dynein to incidence and waveform of the preferred beat types. Outer dynein arms (ODAs) were required for symmetric tip-to-base beats, specific single-headed inner dynein arms (IDAs) were important for asymmetric base-to-tip beats (IDA), and double-headed IDA important for both. This systematic analysis indicates that the prevailing dogma that ODAs drive and IDAs shape the beat is either incomplete or not universal, and establishes new hypotheses for how different species, cell types and individual flagella achieve their necessary beat types. |
 リンク | bioRxiv / PubMed:41279373 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.1 - 17.0 Å |
| 構造データ |  EMDB-71903: 96 nm half 1 consensus map  EMDB-72431: Leishmania 96 nm half 1 composite map  EMDB-72432: 96 nm half 2 composite map  EMDB-72433: Leishmania 96 nm half 2 consensus map  EMDB-72434: Structure of the Leishmania inner dyenin arm A base bound to the DMT  EMDB-72435: Structure of the Leishmania inner dyenin arm A motor domain  EMDB-72436: Structure of the Leishmania inner dyenin arm B base bound to the DMT  EMDB-72437: Structure of the Leishmania inner dyenin arm B motor domain  EMDB-72438: Structure of the Leishmania inner dyenin arm C base bound to the DMT  EMDB-72439: Structure of the Leishmania inner dyenin arm C motor domain  EMDB-72440: Structure of the Leishmania inner dyenin arm D and inner dynein arm G bases bound to the DMT  EMDB-72441: Structure of the Leishmania inner dyenin arm D motor domain  EMDB-72442: Structure of the Leishmania inner dyenin arm E base bound to the DMT  EMDB-72443: Structure of the Leishmania inner dyenin arm E motor domain  EMDB-72444: Structure of the Leishmania inner dyenin arm F base bound to the DMT  EMDB-72445: Structure of the Leishmania inner dyenin arm F motor domains  EMDB-72446: NDRC baseplate protofilament refinement  EMDB-72447: Structure of the distal region of the Leishmania NDRC  EMDB-72448: Structure of the core of the Leishmania Outer Dynein Arm  EMDB-72449: Structure of the Leishmania Outer Dynein Arm motor domains  EMDB-72450: Structure of the Leishmania radial spoke 1 base bound to the DMT  EMDB-72451: Structure of the Leishmania radial spoke 2 base bound to the DMT  EMDB-72452: Structure of the Leishmania radial spoke 3 base portion 1 bound to the DMT  EMDB-72453: Structure of the Leishmania radial spoke 3 portion 2 bound to the DMT  EMDB-72454: Structure of the Leishmania tether-tetherhead complex  EMDB-72563: Leishmania 96 nm half 1 protofilament refinement position 1_1  EMDB-72564: 96 nm half 1 protofilament refinement position 1_2  EMDB-72565: Leishmania 96 nm half 1 protofilament refinement position 1_3  EMDB-72566: Leishmania 96 nm half 1 protofilament refinement position 2_1  EMDB-72567: Leishmania 96 nm half 1 protofilament refinement position 2_2  EMDB-72568: Leishmania 96 nm half 1 protofilament refinement position 2_3  EMDB-72569: Leishmania 96 nm half 1 protofilament refinement position 3_1  EMDB-72570: Leishmania 96 nm half 1 protofilament refinement position 3_2  EMDB-72571: Leishmania 96 nm half 1 protofilament refinement position 3_3  EMDB-72572: Leishmania 96 nm half 1 protofilament refinement position 4_1  EMDB-72573: Leishmania 96 nm half 1 protofilament refinement position 4_2  EMDB-72574: Leishmania 96 nm half 1 protofilament refinement position 4_3  EMDB-72575: Leishmania 96 nm half 1 protofilament refinement position 5_1  EMDB-72576: Leishmania 96 nm half 1 protofilament refinement position 5_2  EMDB-72577: Leishmania 96 nm half 1 protofilament refinement position 5_3  EMDB-72578: Leishmania 96 nm half 1 protofilament refinement position 6_1  EMDB-72579: Leishmania 96 nm half 1 protofilament refinement position 6_2  EMDB-72580: Leishmania 96 nm half 1 protofilament refinement position 6_3  EMDB-72581: Leishmania 96 nm half 1 protofilament refinement position 7_1  EMDB-72582: Leishmania 96 nm half 1 protofilament refinement position 7_2  EMDB-72583: Leishmania 96 nm half 1 protofilament refinement position 7_3  EMDB-72584: Leishmania 96 nm half 1 protofilament refinement position 8_1  EMDB-72585: Leishmania 96 nm half 1 protofilament refinement position 8_2  EMDB-72586: Leishmania 96 nm half 1 protofilament refinement position 8_3  EMDB-72587: Leishmania 96 nm half 1 protofilament refinement position 9_1  EMDB-72588: Leishmania 96 nm half 1 protofilament refinement position 9_2  EMDB-72589: Leishmania 96 nm half 1 protofilament refinement position 9_3  EMDB-72590: Leishmania 96 nm half 1 protofilament refinement position 10_1  EMDB-72591: Leishmania 96 nm half 1 protofilament refinement position 10_2  EMDB-72592: Leishmania 96 nm half 1 protofilament refinement position 10_3  EMDB-72593: Leishmania 96 nm half 2 protofilament refinement position 1_1  EMDB-72594: Leishmania 96 nm half 2 protofilament refinement position 1_2  EMDB-72595: Leishmania 96 nm half 2 protofilament refinement position 1_3  EMDB-72596: Leishmania 96 nm half 2 protofilament refinement position 2_1  EMDB-72597: Leishmania 96 nm half 2 protofilament refinement position 2_2  EMDB-72598: Leishmania 96 nm half 2 protofilament refinement position 2_3  EMDB-72599: Leishmania 96 nm half 2 protofilament refinement position 3_1  EMDB-72600: Leishmania 96 nm half 2 protofilament refinement position 3_2  EMDB-72601: Leishmania 96 nm half 2 protofilament refinement position 3_3  EMDB-72602: Leishmania 96 nm half 2 protofilament refinement position 4_1  EMDB-72603: Leishmania 96 nm half 2 protofilament refinement position 4_2  EMDB-72604: Leishmania 96 nm half 2 protofilament refinement position 4_3  EMDB-72605: Leishmania 96 nm half 2 protofilament refinement position 5_1  EMDB-72606: Leishmania 96 nm half 2 protofilament refinement position 5_2  EMDB-72607: Leishmania 96 nm half 2 protofilament refinement position 5_3  EMDB-72608: Leishmania 96 nm half 2 protofilament refinement position 6_1  EMDB-72609: Leishmania 96 nm half 2 protofilament refinement position 6_2  EMDB-72610: Leishmania 96 nm half 2 protofilament refinement position 6_3  EMDB-72611: Leishmania 96 nm half 2 protofilament refinement position 7_1  EMDB-72612: Leishmania 96 nm half 2 protofilament refinement position 7_2  EMDB-72613: Leishmania 96 nm half 2 protofilament refinement position 7_3  EMDB-72614: Leishmania 96 nm half 2 protofilament refinement position 8_1  EMDB-72615: Leishmania 96 nm half 2 protofilament refinement position 8_2  EMDB-72616: Leishmania 96 nm half 2 protofilament refinement position 8_3  EMDB-72617: Leishmania 96 nm half 2 protofilament refinement position 9_1  EMDB-72618: Leishmania 96 nm half 2 protofilament refinement position 9_2  EMDB-72619: Leishmania 96 nm half 2 protofilament refinement position 9_3  EMDB-72620: Leishmania 96 nm half 2 protofilament refinement position 10_1  EMDB-72621: Leishmania 96 nm half 2 protofilament refinement position 10_2  EMDB-72622: Leishmania 96 nm half 2 protofilament refinement position 10_3 EMDB-72629, PDB-9y6s: |
| 化合物 |  ChemComp-GDP:  ChemComp-MG:  ChemComp-GTP:  ChemComp-ZN:  ChemComp-CA:  ChemComp-ATP: |
| 由来 |
|
 キーワード | STRUCTURAL PROTEIN / flagella / parasite / axoneme / doublet microtubule |
leishmania tarentolae (真核生物)
leishmania mexicana (メキシコリーシュマニア)