CCDC61/VFL3 is a paralog of SAS6 and promotes ciliary functions

Ochi T, Quarantotti V, Lin H, Jullien J, Rosa e Silva I, Boselli F, Barnabas DD, Johnson CM, McLaughlin SH, Freund SMV, Blackford AN, Kimata Y, Goldstein RE, Jackson SP, Blunden TL, Dutcher SK, Gergely F, van Breugel M.

Structure 28, 674-689.e11

Highlights

• CCDC61 is a paralog of SAS6, XRCC4, XLF, and PAXX

• CCDC61 can form protofilaments with a 3-fold screw axis in vitro

• CCDC61 binds to microtubules mainly via its coiled-coil domain

• Microtubule binding of CCDC61 is important for its function in Chlamydomonas

Summary

Centrioles are cylindrical assemblies whose peripheral microtubule array displays a 9-fold rotational symmetry that is established by the scaffolding protein SAS6. Centriole symmetry can be broken by centriole-associated structures, such as the striated fibers in Chlamydomonas that are important for ciliary function. The conserved protein CCDC61/VFL3 is involved in this process, but its exact role is unclear. Here, we show that CCDC61 is a paralog of SAS6. Crystal structures of CCDC61 demonstrate that it contains two homodimerization interfaces that are similar to those found in SAS6, but result in the formation of linear filaments rather than rings. Furthermore, we show that CCDC61 binds microtubules and that residues involved in CCDC61 microtubule binding are important for ciliary function in Chlamydomonas. Together, our findings suggest that CCDC61 and SAS6 functionally diverged from a common ancestor while retaining the ability to scaffold the assembly of basal body-associated structures or centrioles, respectively.