8FH3

Human IFT-A complex structures provide molecular insights into ciliary transport

8FH3 の概要

• エントリーDOI: 10.2210/pdb8fh3/pdb
• EMDBエントリー: 29078
• 分子名称: WD repeat-containing protein 35, Intraflagellar transport protein 122 homolog, WD repeat-containing protein 19, ... (6 entities in total)
• 機能のキーワード: ift-a complex, tulp3, cilia, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 642835.71

構造登録者

Jiang, M.,Palicharla, V.R.,Miller, D.,Hwang, S.H.,Zhu, H.,Hixson, P.,Mukhopadhyay, S.,Sun, J. (登録日: 2022-12-13, 公開日: 2023-02-22, 最終更新日: 2024-11-06)

主引用文献

Jiang, M.,Palicharla, V.R.,Miller, D.,Hwang, S.H.,Zhu, H.,Hixson, P.,Mukhopadhyay, S.,Sun, J.
Human IFT-A complex structures provide molecular insights into ciliary transport.
Cell Res., 33:288-298, 2023

PubMed Abstract: Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. Mutations in IFT subunits lead to numerous ciliopathies involving multiple tissues. However, how IFT complexes assemble and mediate cargo transport lacks mechanistic understanding due to missing high-resolution structural information of the holo-complexes. Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Å. IFT-A adopts a "lariat" shape with interconnected core and peripheral subunits linked by structurally vital zinc-binding domains. TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. We also determine the molecular impacts of disease mutations on complex formation and ciliary transport. Our work reveals IFT-A architecture, sheds light on ciliary transport and IFT train formation, and enables the rationalization of disease mutations in ciliopathies.

PubMed: 36775821
DOI: 10.1038/s41422-023-00778-3

実験手法

ELECTRON MICROSCOPY (4.3 Å)