Biology Reference
In-Depth Information
the questionofwhether EB1 binds to the lattice or seamand provide additional evidence
on the specific question of how human EB1 binds to MTs, (
Alberico, et al., 2013
)
usedMTBindingSim to identify a set of experimental conditions that should distinguish
between a model where EB1 binds strongly to the MT seam with weak to no lattice
binding, and one where EB1 binds to the entire MT with a moderate affinity.
The resulting theoretical binding curves are shown in
Fig. 23.3
BandC(
Alberico,
et al., 2013
). These data lead to the prediction that, if EB1 binds strongly to the seam,
a moderate concentration of EB1 will saturate the available binding sites, and as the
concentration of EB1 increases, the fraction of EB1 that is bound to MTs at a given
MT concentration will fall. In contrast, if EB1 binds to the entire lattice with moderate
or weak affinity, the overall concentration of freeMT sites will change little as the con-
centration of EB1 moves up or down, leading to a situation where the fraction of EB1
bound to MTs stays relatively constant. Note that these graphs are plotted against total
[MT] because calculating the free [MT] cannot be done without making assumptions
about the EB1-MT-binding ratio. Using these simulated binding curves as a guide,
(
Alberico, et al., 2013
) have recently provided strong biochemical evidence that
human EB1 does not bind to the MT seam.
CONCLUSION
MTBindingSim is a software designed to assist researchers in designing and inter-
preting binding experiments as well as in training their intuition about how
MAP-MT-binding interactions will behave. This program has been very helpful
when investigating puzzling MAP-MT-binding behavior and in designing experi-
ments to distinguish between different models of MAP-MT binding. For further in-
formation on how to use MTBindingSim, see the user manual at bindingtutor.org/
mtbindingsim. MTBindingSim is under active development and the developers wel-
come suggestions from other researchers for new features or models for MTBinding-
Sim or for changes to the user interface (see Web site for contact details). A more
general version of MTBindingSim, BindingTutor, for use as an educational tool,
is also currently under development and will be available at bindingtutor.org/bin-
dingtutor when it is completed.
References
Ackmann, M., Wiech, H., &Mandelkow, E. (2000). Nonsaturable binding indicates clustering
of tau on the microtubule surface in a paired helical filament-like conformation.
Journal of
Akhmanova, A. S., & Steinmetz, M. O. (2008). Tracking the ends: A dynamic protein network
controls the fate of microtubule tips.
Nature Reviews. Molecular Cell Biology
,
9
(4),
309-322.
http://dx.doi.org/10.1038/nrm2369
.
Alberico, E. O., Lyons, D. F., Murphy, R. H., Philip, J. T., Duan, A. R., Correia, J. J., &
Goodson, H. V. (2013). Biochemical evidence that human EB1 does not bind preferentially
