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TitleHuman IFT-A complex structures provide molecular insights into ciliary transport.
Journal, issue, pagesCell Res, Vol. 33, Issue 4, Page 288-298, Year 2023
Publish dateFeb 13, 2023
AuthorsMeiqin Jiang / Vivek Reddy Palicharla / Darcie Miller / Sun-Hee Hwang / Hanwen Zhu / Patricia Hixson / Saikat Mukhopadhyay / Ji Sun /
PubMed AbstractIntraflagellar 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 ...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.
External linksCell Res / PubMed:36775821 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 4.3 Å
Structure data

29073

8fgw

EMDB-29073, PDB-8fgw:
Human IFT-A complex structures provide molecular insights into ciliary transport
Method: EM (single particle) / Resolution: 3.7 Å

29078

8fh3

EMDB-29078, PDB-8fh3:
Human IFT-A complex structures provide molecular insights into ciliary transport
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / IFT-A complex / TULP3 / cilia

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