Structural rearrangements in tubulin following microtubule formation

Abstract

Microtubules are essential cytoskeletal structures that mediate several dynamic processes in a cell. To shed light on the structural processes relating to microtubule formation and dynamic instability, we investigated microtubules composed of 15 protofilaments using cryo-electron microscopy, helical image reconstruction and computational modelling. Analysis of the configuration of the ab-tubulin heterodimer shows distinct structural differences in both subunits, and illustrates that the tubulin subunits have different roles in the microtubule lattice. Our modelling data suggest that after GTP hydrolysis microtubules, adopt a conformational state somewhere between a straight protofilament conformation-as found in zinc-induced tubulin sheets-and an outward curved conformation-as found in tubulin-stathmin complexes. The tendency towards a curved conformation seems to be mediated mostly by b-tubulin, whereas a-tubulin resembles a state more related to the straight structure. Our data suggest a possible explanation of dynamic instability of microtubules, and for nucleotide-sensitive microtubule-binding properties of microtubule-associated proteins and molecular motors.

Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase 1act/Tubulin Interaction Is an Important Determinant of Mitotic Stability in Cultured HT1080 Human Fibrosarcoma Cells

“…α and β tubulin are abundant structural proteins and their heterodimer is the structural subunit of microtubules (24). Microtubules have a number of essential cellular functions, including chromosome segregation, the maintenance of cell shape, transport, motility, and organelle distribution (25, 26). The notable structure involving microtubules is the mitotic spindle, which is used by eukaryotic cells to segregate their chromosomes precisely during cell division (27, 28).…”

The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation

“…All data indicated that FKBP52 could neither act as a sequestering protein nor compete for tubulin binding with other proteins that could antagonize the effect of FKBP52; nor could it induce structural rearrangements of tubulin (such as bending of MT) (48), preventing tubulin polymerization. Rather, the data suggest that post‐translational modifications of FKBP52, by compound(s) present in the so‐called “mixed tubulin” could explain the loss of tubulin depolymerization activity obtained with pure tubulin, contrary to the results with mixed tubulin.…”

Altered microtubule dynamics by expression of modified α‐tubulin protein causes right‐handed helical growth in transgenic Arabidopsis plants

“…, 2002, and references therein). The half‐length of GFP‐AtEB1 comets in control cells (Table 4) is estimated to consist of approximately 110 tubulin dimers, as the longitudinal length of the tubulin dimmer in protofilaments is calculated to be approximately 8 nm (Kreb et al. , 2005).…”