IFT-A structure reveals carriages for membrane protein transport into cilia.
Cell
; 185(26): 4971-4985.e16, 2022 12 22.
Article
en En
| MEDLINE
| ID: mdl-36462505
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 ß-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-Aâ
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cilios
/
Cinesinas
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2022
Tipo del documento:
Article