Structural insight into the intraflagellar transport complex IFT-A and its assembly in the anterograde IFT train

  • Nat Commun. 2023 Mar 17;14(1):1506. doi: 10.1038/s41467-023-37208-2.
Yuanyuan Ma  #  1  2 ,  Jun He  #  1  2 ,  Shaobai Li  1  2 ,  Deqiang Yao  3 ,  Chenhui Huang  1  2 ,  Jian Wu  4  5 ,  Ming Lei  6  7  8
Affiliations
  • 1. Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
  • 2. Shanghai Institute of Precision Medicine, Shanghai, 200125, China.
  • 3. Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • 4. Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. [email protected].
  • 5. Shanghai Institute of Precision Medicine, Shanghai, 200125, China. [email protected].
  • 6. Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. [email protected].
  • 7. Shanghai Institute of Precision Medicine, Shanghai, 200125, China. [email protected].
  • 8. State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. [email protected].
  • # Contributed equally.
PMID: 36932088 DOI: 10.1038/s41467-023-37208-2
Abstract

Intraflagellar transport (IFT) trains, the Polymers composed of two multi-subunit complexes, IFT-A and IFT-B, carry out bidirectional intracellular transport in cilia, vital for cilia biogenesis and signaling. IFT-A plays crucial roles in the ciliary import of membrane proteins and the retrograde cargo trafficking. However, the molecular architecture of IFT-A and the assembly mechanism of the IFT-A into the IFT trains in vivo remains elusive. Here, we report the cryo-electron microscopic structures of the IFT-A complex from protozoa Tetrahymena thermophila. We find that IFT-A complexes present two distinct, elongated and folded states. Remarkably, comparison with the in situ cryo-electron tomography structure of the anterograde IFT train unveils a series of adjustments of the flexible arms in apo IFT-A when incorporated into the anterograde train. Our results provide an atomic-resolution model for the IFT-A complex and valuable insights into the assembly mechanism of anterograde IFT trains.

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