8J07

96nm repeat of human respiratory doublet microtubule and associated axonemal complexes

これはPDB形式変換不可エントリーです。

8J07 の概要

• エントリーDOI: 10.2210/pdb8j07/pdb
• EMDBエントリー: 35888 36891 36895 40220 41271
• 分子名称: Dynein regulatory complex subunit 4, Cilia- and flagella-associated protein 95, Outer dynein arm-docking complex subunit 2, ... (109 entities in total)
• 機能のキーワード: cilia, microtubule, dynein, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 974
• 化学式量合計: 53328110.33

構造登録者

Gui, M.,Brown, A. (登録日: 2023-04-09, 公開日: 2023-07-26, 最終更新日: 2025-09-17)

主引用文献

Walton, T.,Gui, M.,Velkova, S.,Fassad, M.R.,Hirst, R.A.,Haarman, E.,O'Callaghan, C.,Bottier, M.,Burgoyne, T.,Mitchison, H.M.,Brown, A.
Axonemal structures reveal mechanoregulatory and disease mechanisms.
Nature, 618:625-633, 2023

PubMed Abstract: Motile cilia and flagella beat rhythmically on the surface of cells to power the flow of fluid and to enable spermatozoa and unicellular eukaryotes to swim. In humans, defective ciliary motility can lead to male infertility and a congenital disorder called primary ciliary dyskinesia (PCD), in which impaired clearance of mucus by the cilia causes chronic respiratory infections. Ciliary movement is generated by the axoneme, a molecular machine consisting of microtubules, ATP-powered dynein motors and regulatory complexes. The size and complexity of the axoneme has so far prevented the development of an atomic model, hindering efforts to understand how it functions. Here we capitalize on recent developments in artificial intelligence-enabled structure prediction and cryo-electron microscopy (cryo-EM) to determine the structure of the 96-nm modular repeats of axonemes from the flagella of the alga Chlamydomonas reinhardtii and human respiratory cilia. Our atomic models provide insights into the conservation and specialization of axonemes, the interconnectivity between dyneins and their regulators, and the mechanisms that maintain axonemal periodicity. Correlated conformational changes in mechanoregulatory complexes with their associated axonemal dynein motors provide a mechanism for the long-hypothesized mechanotransduction pathway to regulate ciliary motility. Structures of respiratory-cilia doublet microtubules from four individuals with PCD reveal how the loss of individual docking factors can selectively eradicate periodically repeating structures.

PubMed: 37258679
DOI: 10.1038/s41586-023-06140-2

実験手法

ELECTRON MICROSCOPY (4.1 Å)