Speaker
Description
Microtubules are hollow cylindrical cytoskeletal polymers of laterally associated protofilaments that contain head-to-tail aligned ɑ/β-tubulin heterodimers. While the exposed exterior is within reach for proteins, the mechanism regulating the accessibility of the confined micrometer-long microtubule lumen for the long-observed luminal particles remains unknown. Here, we employed structural analysis, force microscopy, and in vitro reconstitution to reveal that tubulin family proteins (i.e., isotypes) regulate the microtubule accessibility for luminal enzymes via the force-sensitive reversible protofilament separation, referred to as lattice breathing. Computational simulation further demonstrates that the strength of inter-protofilament lateral interactions determines the degree of lattice breathing and luminal accessibility. Microtubule deformation surpassing the lattice stress threshold creates gaps between adjacent protofilaments, which enhance protein entry into the lumen. Together, our findings reveal the mechanical plasticity of non-covalent interactions between tubulin subunits, conferring force sensitivity to the microtubule lattice and rendering the energy barrier for protein to access the lumen.
