# IFT-A structure reveals carriages for membrane protein transport into cilia

Article · Sophie J. Hesketh, Aakash Gautam Mukhopadhyay, Dai Nakamura, Katerina Toropova, Anthony J. Roberts

- Archive id: doi:10.1016/j.cell.2022.11.010
- Published: 2022-12-01
- Venue: Cell
- DOI: https://doi.org/10.1016/j.cell.2022.11.010
- PMID: 36462505
- Citations: 83
- Source URL: https://doi.org/10.1016/j.cell.2022.11.010
- PDF: http://www.cell.com/article/S0092867422014222/pdf
- Provenance: openalex

## Abstract

Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes, interacts with IFT-B, and uses an array of β-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-A⋅TULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK-the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A's distinct functions, provide a blueprint for IFT-A in the train, and shed light on how IFT evolved from a proto-coatomer ancestor.

_Abstract reproduced under CC-BY (publisher license, via OpenAlex)._

Topics: [AI Protein Design & Structure Prediction](https://space-kitty.com/topics/protein-design)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.