Figure 7: The role of A-lattice seams in MT catastrophe.

In 13–3 B-lattice single-seam MTs PFs form strong lateral bonds (left panel) except at the A-lattice contacts of the MT seam (middle panel). B-lattice MTs enriched with A-lattice seams have more of the weaker contacts (right panel). (1) Uncapping: loss of GTP tubulin uncaps the MT. Detachment of tubulin from most of the B-lattice end is limited by the two strong lateral interactions on both sides of the heterodimer (left panel). Because of the spiral arrangement of heterodimers one heterodimer at the end will only make one lateral B-lattice contact (middle panel). At A-lattice seams this contact will be weaker and the heterodimer will detach more easily. In a MT enriched for A-lattice the MT end will become crenellated and more heterodimers will have only two weaker half lateral interactions, increasing their rate of detachment (right panel). (2) Crack propagation: crack formation breaks lateral contacts in both A- and B-lattices enhancing the dissociation of the GTP tubulin heterodimers in the cap as more heterodimers become exposed with fewer lateral contacts. Cracks propagate preferentially along the less stable lateral contacts between PFs in A-lattice seams. (3) GDP lattice shrinkage: shrinkage of GDP lattice proceeds via outward bending of the PFs in both the B-lattice (left hand) and A-lattice seams (middle, right hand panels). Weaker lateral contacts in A-lattice seams promote this process. At minus ends this process appears to limit shrinkage rates, possibly because of exposed GTP alpha tubulin. Plus ends expose GDP beta tubulin and PF unpeeling is then not limiting the depolymerization rate. Mechanical constraint of the MT, for example by rigor-bound kinesin motors attached to a surface, would inhibit both crack formation (step 2) and PF bending (step 3), inhibiting the transition to rapid post-catastrophe shrinkage of GDP-MT lattice (black top hats). Thus, catastrophe has two distinct steps: dissociation (or hydrolysis) of the GTP subunits forming the cap, followed by an allosteric change with bending of the PFs. A-lattice seams enhance both processes, so that seams promote both the loss of the GTP cap and the subsequent transition to rapid shrinkage.