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bioRxiv · 10.1101/2024.11.13.623454

Structural insights into SSNA1 self-assembly and its microtubule binding for centriole maintenance

Abstract

SSNA-1 is a fibrillar protein localized at the area where dynamic microtubule remodeling occurs including centrosomes. Despite the important activities of SSNA1 to microtubules such as nucleation, co-polymerization, and lattice sharing microtubule branching, the underlying molecular mechanism have remained unclear due to a lack of structural information. Here, we determined the cryo-EM structure of C. elegans SSNA-1 at 4.55 [A] resolution and evaluated its role during embryonic development in C. elegans. We found that SSNA1 forms an anti-parallel coiled-coil, and its self-assembly is facilitated by the overhangs of 16 residues at its C-terminus, which dock on the adjacent coiled-coil to form a triple-stranded helical junction. Notably, the microtubule-binding region is within the triple-stranded junction, highlighting that self-assembly of SSNA-1 facilitates effective microtubule interaction by creating hubs along a fibril. Furthermore, our genetical analysis elucidated that deletion of SSNA-1 resulted in a significant reduction in embryonic viability and the formation of multipolar spindles during cell division. Interestingly, when the ability of SSNA-1 self-assembly was impaired, embryonic viability stayed low, comparable to that of the knockout strain. Our study provides molecular insights into the self-assembly mechanisms of SSNA-1, shedding light on its role in controlling microtubule binding and cell division through the regulation of centriole stability.

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BibTeXRIS

Agostini, L., Pfister, J., Basnet, N., Ding, J., Zhang, R., Biertumpfel, C., O'Connell, K., Mizuno, N.. 2024-11-15. Structural insights into SSNA1 self-assembly and its microtubule binding for centriole maintenance. https://doi.org/10.1101/2024.11.13.623454

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