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TitleThe molecular structure of IFT-A and IFT-B in anterograde intraflagellar transport trains.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 5, Page 584-593, Year 2023
Publish dateJan 2, 2023
AuthorsSamuel E Lacey / Helen E Foster / Gaia Pigino /
PubMed AbstractAnterograde intraflagellar transport (IFT) trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFT-A and IFT-B proteins that link structural and signaling cargos to ...Anterograde intraflagellar transport (IFT) trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFT-A and IFT-B proteins that link structural and signaling cargos to microtubule motors for import into cilia. It remains unknown how the IFT-A/-B proteins are arranged into complexes and how these complexes polymerize into functional trains. Here we use in situ cryo-electron tomography of Chlamydomonas reinhardtii cilia and AlphaFold2 protein structure predictions to generate a molecular model of the entire anterograde train. We show how the conformations of both IFT-A and IFT-B are dependent on lateral interactions with neighboring repeats, suggesting that polymerization is required to cooperatively stabilize the complexes. Following three-dimensional classification, we reveal how IFT-B extends two flexible tethers to maintain a connection with IFT-A that can withstand the mechanical stresses present in actively beating cilia. Overall, our findings provide a framework for understanding the fundamental processes that govern cilia assembly.
External linksNat Struct Mol Biol / PubMed:36593313 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution9.9 - 20.7 Å
Structure data

15977

8bd7

EMDB-15977: IFTB1 subcomplex of anterograde intraflagellar transport trains (Chlamydomonas reinhardtii)
PDB-8bd7: IFTB1 subcomplex of anterograde Intraflagellar transport trains (Chlamydomonas reinhardtii)
Method: EM (subtomogram averaging) / Resolution: 9.9 Å

EMDB-15978: Masked refinement of the IFTB1 subcomplex within anterograde intraflagellar trains in Chlamydomonas reinhardtii cilia
Method: EM (subtomogram averaging) / Resolution: 9.9 Å

EMDB-15979: Masked refinement of the IFTB2 subcomplex within anterograde intraflagellar trains in Chlamydomonas reinhardtii cilia
Method: EM (subtomogram averaging) / Resolution: 11.5 Å

15980

8bda

EMDB-15980: IFTA complex in anterograde Intraflagellar transport trains (Chlamydomonas reinhardtii)
PDB-8bda: IFTA complex in anterograde intraflagellar transport trains (Chlamydomonas reinhardtii)
Method: EM (subtomogram averaging) / Resolution: 20.7 Å

EMDB-16014: Subtomogram average of complete IFTB complex (before focussed refinements of IFTB1/2) for consensus map generation
Method: EM (subtomogram averaging) / Resolution: 14.1 Å

Source
  • chlamydomonas reinhardtii (plant)
KeywordsPROTEIN TRANSPORT / Cilia / IFT / Intraflagellar / transport

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