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-Structure paper
| タイトル | IFT-A structure reveals carriages for membrane protein transport into cilia. |
|---|---|
| ジャーナル・号・ページ | Cell, Vol. 185, Issue 26, Page 4971-4985.e16, Year 2022 |
| 掲載日 | 2022年12月22日 |
著者 | Sophie J Hesketh / Aakash G Mukhopadhyay / Dai Nakamura / Katerina Toropova / Anthony J Roberts / ![]() |
| PubMed 要旨 | 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) ...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. |
リンク | Cell / PubMed:36462505 |
| 手法 | EM (単粒子) |
| 解像度 | 3.5 - 8.0 Å |
| 構造データ | EMDB-15954, PDB-8bbe: EMDB-15955, PDB-8bbf: ![]() PDB-8bbg: |
| 由来 |
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キーワード | TRANSPORT PROTEIN / cilia / intraflagellar transport / membrane protein import / complex |
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