Journal
CELL
Volume 185, Issue 26, Pages 4986-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2022.11.033
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Funding
- Charles A. King Trust Postdoctoral Research Fellowship
- NIGMS [GM141109, GM143183]
- Smith Family Foundation
- Pew Charitable Trusts
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This study determined the structures of native IFT-A complexes using cryo-EM and found that subcomplex rearrangements enable IFT-A to polymerize on anterograde IFT trains. The study also discovered that binding of IFT-A to IFT-B shields the preferred lipid-binding interface and orients a network of b-propeller domains towards the ciliary membrane, capable of accommodating diverse cargoes.
Intraflagellar transport (IFT) is the highly conserved process by which proteins are transported along ciliary microtubules by a train-like polymeric assembly of IFT-A and IFT-B complexes. IFT-A is sandwiched between IFT-B and the ciliary membrane, consistent with its putative role in transporting transmembrane and membrane-associated cargoes. Here, we have used single-particle analysis electron cryomicroscopy (cryo-EM) to determine structures of native IFT-A complexes. We show that subcomplex rearrangements enable IFT-A to polymerize laterally on anterograde IFT trains, revealing a cooperative assembly mechanism. Surprisingly, we discover that binding of IFT-A to IFT-B shields the preferred lipid-binding interface from the ciliary membrane but orients an interconnected network of b-propeller domains with the capacity to accommodate diverse cargoes toward the ciliary membrane. This work provides a mechanistic basis for understanding IFT-train assembly and cargo interactions.
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