Microtubule nucleation visualized at high resolution
Life & Medical Sciences
Microtubules are tube-shaped filaments that serve in cells as tracks for molecular motors and are essential for segregating the genetic material during cell divsion. In human cells, the growth of microtubules starts in a highly regulated manner from a large protein complex called the γ-tubulin ring complex (γTuRC). Using cryo-electron microscopy, we have visualized for the first time at high resolution how this complex "nucleates" the growth of a microtubule. Our work revealed that the complex undergoes a large structural change as the microtubule begins assembling, a change that ensures that γTuRC can enforce the correct tube-like structure of the microtubule. This large-scale structural change of γTuRC is likely the target of regulation in cells. This work provides new insight into the poorly understood molecular mechanism of the control of microtubule polymerization and its regulation in cells and opens up new possibilities to target incorrect microtubule mass regulation in disease.
Left: High-resolution cryo-electron microscopy structure of the γ-tubulin ring complex (γTuRC, at the bottom) with the first two layers of tubulins (tubulin dimer in grey and yellow, shown at lower resolution) on top. Right: Fluorescence microscopy image of a long microtubule (red) having been nucleated from a single γTuRC (cyan) shown at much lower magnification. Modified from Brito, Serna et al., 2024.
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