The name is absent



GTP hydrolysis and dynamic instability

The main difference between α- and β-tubulins is in binding GTP. α-bound GTP
is effectively sequestered - not exchanged and not hydrolyzed - but
β-bound
GTP is labile - exchangeable in the free dimer and hydrolyzed to
(non-exchangeable) guanosine diphosphate (GDP) in the protofilament
(
Weisenberg et al., 1976). A significant amount of the free energy of this
hydrolysis goes into the microtubule via a conformational change of the tubulin
dimer (
Caplow et al., 1994). Although the hydrolysis reaction is closely coupled to
microtubule assembly (
Carlier & Pantaloni, 1981; Stewart et al., 1990), its
consequence is to destabilize the structure. Experiments indicate that
unhydrolyzed GTP-tubulin is limited to the last layer of subunits at the end of a
microtubule (
Voter et al., 1991; Walker et al., 1991; Drechsel & Kirschner, 1994).
The usual interpretation is that this layer acts as a “GTP-cap”, keeping an
otherwise unstable microtubule intact (
Mitchison & Kirschner, 1984).

Microtubule dynamic instability arises from the hydrolysis of GTP bound to the
β-monomer of the tubulin dimer. The released energy of 0.4 eV from
GTP-hydrolysis triggers a conformational change in the tubulin molecule (
Hyman
et al., 1992
) that eventually destabilizes the aggregate (Tran et al., 1997) and
causes microtubule disassemble into protofilaments of GDP-bound tubulin that
curve away from the microtubule axis.
Fygenson (2001) suggests that the
unfolding of N-terminal domain called
entropic bristle domain (EBD) of the tubulin
molecule localized in the microtubule interior leads to disassembly of the
microtubule into protofilaments. It is shown that such a change can destabilize
the aggregate in a manner consistent with structural data (
Mandelkow et al.,
1991
). The hypothesis not only explains the hydrolysis-associated change in
microtubule supertwist
(Hyman et al., 1995) but also provides a unifying
explanation for the effects of temperature (
Fygenson et al., 1994) and glycerol
(
Fygenson, 1995) on microtubule disassembly rates.

63



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