Significance
This study presents a direct visualization of the microtubule-p150glued(CAP-Gly) complex by cryo-EM and seeks to describe the molecular mechanism of the control of tubulin dynamics by p150 CAP-Gly. It highlights the neutralization of the acidic tubulin surface by the basic extensions of CAP-Gly, resulting in the activation of tubulin polymerization. In the condition where the lateral association is impeded (i.e., at low temperature), the extended CAP-Gly domain induces tubulin dimers to connect longitudinally. The two directional modes of self-association of tubulin suggest a foundation for its dynamic behavior at the tip of microtubules and its regulation.
The cilium is an organelle used for motility and cellular signaling. Intraflagellar transport (IFT) is a process to move ciliary building blocks and signaling components into the cilium. How IFT controls the movement of ciliary components is currently poorly understood. IFT172 is the largest IFT subunit essential for ciliogenesis. Due to its large size, the characterization of IFT172 has been challenging. Using giant unilamellar vesicles (GUVs), we show that IFT172 is a membrane-interacting protein with the ability to remodel large membranes into small vesicles. Purified IFT172 has an architecture of two globular domains with a long rod-like protrusion, resembling the domain organization of coatomer proteins such as COPI-II or clathrin. IFT172 adopts two different conformations that can be manipulated by lipids or detergents: 1) an extended elongated conformation and 2) a globular closed architecture. Interestingly, the association of IFT172 with membranes is mutually exclusive with IFT57, implicating multiple functions for IFT172 within IFT.
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