8BBE

Structure of the IFT-A complex; IFT-A2 module

Summary for 8BBE

• Entry DOI: 10.2210/pdb8bbe/pdb
• Related: 8BBF 8BBG
• EMDB information: 15954 15955
• Descriptor: Intraflagellar transport protein 122 homolog, SNAP-tag,Tetratricopeptide repeat protein 21B, WD repeat-containing protein 35, ... (4 entities in total)
• Functional Keywords: cilia, intraflagellar transport, membrane protein import, complex, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 470019.20

Authors

Hesketh, S.J.,Mukhopadhyay, A.G.,Nakamura, D.,Toropova, K.,Roberts, A.J. (deposition date: 2022-10-12, release date: 2022-12-21, Last modification date: 2024-07-24)

Primary citation

Hesketh, S.J.,Mukhopadhyay, A.G.,Nakamura, D.,Toropova, K.,Roberts, A.J.
IFT-A structure reveals carriages for membrane protein transport into cilia.
Cell, 185:4971-, 2022

PubMed 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.

PubMed: 36462505
DOI: 10.1016/j.cell.2022.11.010

Experimental method

ELECTRON MICROSCOPY (3.5 Å)