Microtubule dynamics are defined by conformations and stability of clustered protofilaments DOI Creative Commons
Maksim Kalutskii, Helmut Grubmüller, Vladimir A. Volkov

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(22)

Published: May 29, 2025

Microtubules are dynamic cytoskeletal polymers that add and lose tubulin dimers at their ends. Microtubule growth, shortening, transitions between them linked to GTP hydrolysis. Recent evidence suggests flexible protofilaments microtubule ends adopt a variety of shapes, complicating structural analysis using conventional techniques. Therefore, the link hydrolysis, protofilament structure polymerization state is poorly understood. Here, we investigate conformational dynamics coarse-grained modeling supported by atomistic simulations cryoelectron tomography. We show individual bent organize in clusters, transient precursors straight lattice, with GTP-bound showing elevated more persistent cluster formation. Differences mechanical properties GTP- GDP-protofilaments result differences intracluster tension, determining both clustering propensity length. propose selection favors long-lived clusters short GTP-protofilaments prone forming lattice accommodating new dimers. Conversely, trapped states unevenly long stiff shortening. conclude key phenomenon links hydrolysis single tubulins entire microtubule.

Language: Английский

Phosphorylation at the Helm: Kinase‐Mediated Regulation of Primary Cilia Assembly and Disassembly DOI Creative Commons
Andrea Lacigová, Lukáš Čajánek

Cytoskeleton, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

The primary cilium serves as an antenna of most vertebrate cells and is important for conveying cues from several signaling pathways into appropriate cellular responses during development homeostasis. Cilia assembly disassembly processes are thought to be strictly controlled; however, the precise nature molecular events underlying this control still awaits full resolution. Through their enzymatic activity, kinases function flexible yet highly controllable regulators a vast variety processes. Their activity ranges cell cycle regulation motility, signal transduction, metabolism. This review focuses on emerging role in cilia biology. We underscore functions formation, maintenance, resorption while examining available models respective mechanisms actions.

Language: Английский

Citations

0
Microtubule dynamics are defined by conformations and stability of clustered protofilaments DOI Creative Commons
Maksim Kalutskii, Helmut Grubmüller, Vladimir A. Volkov

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(22)

Published: May 29, 2025

Microtubules are dynamic cytoskeletal polymers that add and lose tubulin dimers at their ends. Microtubule growth, shortening, transitions between them linked to GTP hydrolysis. Recent evidence suggests flexible protofilaments microtubule ends adopt a variety of shapes, complicating structural analysis using conventional techniques. Therefore, the link hydrolysis, protofilament structure polymerization state is poorly understood. Here, we investigate conformational dynamics coarse-grained modeling supported by atomistic simulations cryoelectron tomography. We show individual bent organize in clusters, transient precursors straight lattice, with GTP-bound showing elevated more persistent cluster formation. Differences mechanical properties GTP- GDP-protofilaments result differences intracluster tension, determining both clustering propensity length. propose selection favors long-lived clusters short GTP-protofilaments prone forming lattice accommodating new dimers. Conversely, trapped states unevenly long stiff shortening. conclude key phenomenon links hydrolysis single tubulins entire microtubule.

Language: Английский

Citations

0