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TitleIntegrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 5741, Year 2023
Publish dateSep 15, 2023
AuthorsAvrin Ghanaeian / Sumita Majhi / Caitlyn L McCafferty / Babak Nami / Corbin S Black / Shun Kai Yang / Thibault Legal / Ophelia Papoulas / Martyna Janowska / Melissa Valente-Paterno / Edward M Marcotte / Dorota Wloga / Khanh Huy Bui /
PubMed AbstractCilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein ...Cilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein regulatory complex (N-DRC), which links adjacent doublet microtubules and regulates and coordinates the activity of outer doublet complexes. Despite its critical role in cilia motility, the assembly and molecular basis of the regulatory mechanism are poorly understood. Here, using cryo-electron microscopy in conjunction with biochemical cross-linking and integrative modeling, we localize 12 DRC subunits in the N-DRC structure of Tetrahymena thermophila. We also find that the CCDC96/113 complex is in close contact with the DRC9/10 in the linker region. In addition, we reveal that the N-DRC is associated with a network of coiled-coil proteins that most likely mediates N-DRC regulatory activity.
External linksNat Commun / PubMed:37714832 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging)
Resolution3.6 - 21.2 Å
Structure data

41189

8tek

EMDB-41189, PDB-8tek:
Baseplate of Nexin-dynein regulatory complex from Tetrahymena thermophila
Method: EM (single particle) / Resolution: 3.6 Å

41251

8th8

EMDB-41251, PDB-8th8:
Linker domain of Nexin-dynein regulatory complex from Tetrahymena thermophila
Method: EM (single particle) / Resolution: 7.4 Å

EMDB-41270: Focused refinement of the N-DRC from the Tetrahymena WT subtomo
Method: EM (subtomogram averaging) / Resolution: 21.2 Å

41284

8tid

EMDB-41284, PDB-8tid:
Combined linker domain of N-DRC and associated proteins Tetrahymena
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-41375: Linker domain of N-DRC complex from Tetrahymena thermophila
Method: EM (single particle) / Resolution: 7.6 Å

EMDB-41376: 96nm repeat of Doublet microtubule from Tetrahymena thermophila
Method: EM (single particle) / Resolution: 5.54 Å

EMDB-41504: DRC9/10 baseplate from Tetrahymena thermophila
Method: EM (single particle) / Resolution: 7.6 Å

Source
  • tetrahymena thermophila (eukaryote)
KeywordsPROTEIN BINDING / complex / Cilia / axoneme / nexin-dynein regulatory complex / STRUCTURAL PROTEIN / dynein

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