Figure 6. Mechanism of MT stabilization by Taxol.

(A and B) Taxol-bound tubulin in the straight conformation associated into PFs forming either the zinc-induced sheet lattice [100] (A) or the MT lattice (B). Each panel shows a single-layer fragment of each lattice and MT lattice (B) is viewed from the lumen. Taxol stabilizes each lattice against cold temperature depolymerization and aging. The PFs in the sheet (A) run in an anti-parallel fashion and in MTs (B) in a parallel fashion, with a stagger determining helical rise of the MT cylinder. The PF polarity is indicated with (+) and (−) signs and with the arrows running along the PF ridges (outside crests in the MT context). Tubulin backbone and nucleotides are shown as wires, Taxol as sticks, and zinc as balls (Chimera [107]); PDB structure identifiers and the color-coding of features are indicated; this depiction uses fading to indicate depth. (C) Close-up view on the Taxol-binding site and its perturbation upon tubulin transition from straight (gray) to bent (magenta) conformation. Multiple straight tubulin structures (with and without Taxol) are aligned on the β-tubulin subunit together with multiple bent tubulin structures, determined by cryo-EM or X-ray crystallography. Tubulins are shown with backbone stick representation and Taxol with molecular surface representation. The PDB identifiers are listed according to tubulin conformation; 6BOC can be found in both columns, since it represents a complex containing two, Taxol-bound (straight) and unbound (bent) tubulin dimers. Straight-to-bent conformational transition moves the S9–S10 loop and the M loop toward Taxol-binding pocket (curved arrows), which severely clashes with Taxol density (asterisks). Only in the straight conformation the M loop is in the position compatible with forming lateral contacts (boxed with the broken line) in both MTs and zinc-induced sheets.