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. Author manuscript; available in PMC: 2010 Jun 9.
Published in final edited form as: Nature. 2008 Jan 17;451(7176):363–367. doi: 10.1038/nature06482

Figure 4. Proposed mechanism of severing by spastin and effects of disease mutations.

Figure 4

a, Proposed mechanism for microtubule-severing by spastin. The spastin AAA core is shown in cyan with pore loops 1, 2 and 3 highlighted in red and numbered in the figure. The MIT domains are shown as gold ovals. The valency of the interaction of the MIT domains with the microtubule is unknown. On the basis of affinity measurements, it is likely that not all MIT domains are engaged with the microtubule (the potentially unengaged MIT domain is shown hatched). The tubulin heterodimers forming the microtubule are shown in green as a ribbon representation, whereas the C-terminal tubulin tails are shown in red cartoon representation. b, Left, molecular surface of spastin (face A). One protomer is shown in a ribbon representation and residues mutated in HSP patients are shown as violet spheres. Right, in addition to mapping to the pore loops (S589Y, R601L, P631L), disease mutations can interfere with ATP binding (F522C, N527K, K529R) and protomer–protomer interactions (D697N, R704Q, R641C, R601L, P631L). G511R maps to a loop on face A where it could destabilize protomer–protomer interactions and/or the microtubule-binding interface (Supplementary Fig. 4).