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