Beating of motile cilia is essential for many physiological processes in mammals, such as development, clearance of epithelial mucus and sperm movement. The power-generating core of cilia is the axoneme, an assembly of dynein-decorated doublet microtubules (DMTs) arranged in a typical ‘9 + 2’ architecture in most motile cilia. Dyneins that periodically connect neighboring DMTs generate force by ATP-fueled coordinated power strokes. Although the general structure of the axoneme is known, many details have remained unclear. Work by Alan Brown, Dominic P. Norris, Sudipto Roy and colleagues published in Cell now reports the application of cryo-electron microscopy to determine many of those molecular details. The authors purified motile cilia from bovine tracheae and managed to obtain a structural map of the essential 48-nm repeat region at 3.4 Å resolution. Microtubule inner proteins (MIPs) are known to decorate the luminal surfaces of DMTs in periodic patterns, but their exact identity and position in mammals was unknown. The reported structure reveals 29 unique MIPs, some of which were previously uncharacterized. Tektins, filament-forming proteins that have been observed in different positions in previous studies, are shown to reside inside the DMT lumens. The authors also resolved a pentameric docking complex (the ODA-DC) that attaches dyneins to DMTs, and identified the paralogous DMT-spanning proteins Pierce1 and Pierce2 as linkers between the external ODA-DCs and internal MIPs. Genetic ablation of both Pierce1 and Pierce2 caused ciliopathy-like phenotypes in zebrafish and mice, which underscores the importance of these scaffolding proteins.
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