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Figure 6.
Figure 6. Structural Model of the Mechanism of MT
Depolymerization by KIF-M(A) ADP bound KIF-M (light blue) binds
to the side wall of the MT.(B) The neck helix (green) interferes
with the M loop in the interprotofilament groove, and KIF-M
cannot bind tightly to the side wall of the MT. The nucleotide
binding pocket is trapped in the open state. Thus, ATP bound
KIF-M diffuses along the MT protofilament.(C) When KIF-M reaches
the end of the MT, the curved conformation of the protofilament
allows full contact with KIF-M. The L8 loop (blue) closes the
nucleotide binding pocket and ATP hydrolysis takes place. The
neck helix destabilizes the lateral interaction of the
protofilament, and the KVD-finger (red) stabilizes the curved
conformation of the interdimer groove.(D) Tubulin dimer or
oligomer is spontaneously released from the curved end of the
protofilament.Hydrolysis of ATP on the tubulin dimer (or
oligomer) releases KIF-M and the next cycle starts.
Alternatively, only the tubulin dimer is released and KIF-M
remains on the protofilament, sliding back to release the next
tubulin dimer processively (C′ and D′). The same mechanism
can also explain depolymerization from the minus end of MT (E).
Dimerization of KIF-M is not required for this mechanism, but
will further increase the depolymerization activity (F).
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