8FGW

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

Summary for 8FGW

• Entry DOI: 10.2210/pdb8fgw/pdb
• EMDB information: 29073
• Descriptor: WD repeat-containing protein 35, Intraflagellar transport protein 122 homolog, WD repeat-containing protein 19, ... (7 entities in total)
• Functional Keywords: ift-a complex, tulp3, cilia, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 767886.57

Authors

Jiang, M.,Palicharla, V.R.,Miller, D.,Hwang, S.H.,Zhu, H.,Hixson, P.,Mukhopadhyay, S.,Sun, J. (deposition date: 2022-12-12, release date: 2023-02-22, Last modification date: 2023-04-12)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.7 Å)