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

Yuanyuan Ma; Jun He; Shaobai Li; Deqiang Yao; Chenhui Huang; Jian Wu; Ming Lei

doi:10.1038/s41467-023-37208-2

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.

Authors

Yuanyuan Ma^#^{1

2}, Jun He^#^{1

2}, Shaobai Li^{1

2}, Deqiang Yao³, 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. wujian@shsmu.edu.cn.
⁵ Shanghai Institute of Precision Medicine, Shanghai, 200125, China. wujian@shsmu.edu.cn.
⁶ Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. leim@shsmu.edu.cn.
⁷ Shanghai Institute of Precision Medicine, Shanghai, 200125, China. leim@shsmu.edu.cn.
⁸ State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. leim@shsmu.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Transport
Cilia* / metabolism
Cryoelectron Microscopy
Electron Microscope Tomography
Flagella / metabolism
Signal Transduction*