Distinct architecture and composition of mouse axonemal radial spoke head revealed by cryo-EM

ABSTRACT: Significance The radial spoke (RS) transmits mechanochemical signals from the central pair (CP) to axonemal dynein arms to coordinate ciliary motility. The RS head, the key CP interaction domain, differs dramatically in morphology between protozoa and metazoa despite the conservation of components in evolution. In this work, we show that the murine RS head is compositionally distinct from that of Chlamydomonas and describe the cryo-EM structure of its core complex at 3.2-Å resolution. Our results provide a blueprint for understanding not only the allosteric coordination within the complex and the mechanism of the RS–CP interaction but also the etiology of numerous RS head gene mutations that have been linked to primary ciliary dyskinesia. The radial spoke (RS) heads of motile cilia and flagella contact projections of the central pair (CP) apparatus to coordinate motility, but the morphology is distinct for protozoa and metazoa. Here we show the murine RS head is compositionally distinct from that of Chlamydomonas. Our reconstituted murine RS head core complex consists of Rsph1, Rsph3b, Rsph4a, and Rsph9, lacking Rsph6a and Rsph10b, whose orthologs exist in the protozoan RS head. We resolve its cryo-electron microscopy (cryo-EM) structure at 3.2-Å resolution. Our atomic model further reveals a twofold symmetric brake pad-shaped structure, in which Rsph4a and Rsph9 form a compact body extended laterally with two long arms of twisted Rsph1 β-sheets and potentially connected dorsally via Rsph3b to the RS stalk. Furthermore, our modeling suggests that the core complex contacts the periodic CP projections either rigidly through its tooth-shaped Rsph4a regions or elastically through both arms for optimized RS–CP interactions and mechanosignal transduction.

SUBMITTER: Zheng W 

PROVIDER: S-EPMC7848523 | biostudies-literature |

REPOSITORIES: biostudies-literature