Biomedical Engineering Reference
In-Depth Information
Mikhailenko. et. al.,. 2010).. Motility. requires. asymmetric. hydrolysis. of. ATP. by. the. two.
motor. heads. that. results. in. generation. of. an. 8.nm. step. size. on. the. microtubule. track.
(Block,. 1995,. 1996;. Higuchi. et. al.,. 2004).. Mechanistic. details. of. how. kinesin. advances.
favor. a. hand-over-hand. stepping. mechanism. (Cross,. 1995;. Asbury. et. al.,. 2003;. Yildiz.
et.al.,.2004);.however,.an.inchworm.mechanism.is.also.consistent.with.data.that.include.
neck.rotation.measurements.(Hua.et.al.,.2002)..The.step.size.corresponds.as.well.to.the.
distance. between. alternating. heterodimeric. α/β-tubulin. subunits. that. are. arranged.
longitudinally. to. form. protoilaments. of. the. microtubule. lattice. (Nogales. et. al.,. 1998)..
For. kinesins. and. Klps,. the. direction. of. movement. is. largely. dictated. by. the. sequence.
of.the.neck.domain.(Endow.and.Waligora,.1998;.Sablin.et.al.,.1998;.Heuston.et.al.,.2010).
Processivity.refers.to.the.amount.of.time.that.a.motor.stays.on.its.track.before.dissoci-
ating..This.parameter.incorporates.the.distance.traveled.and.relects.the.number.of.ATP.
cycles.occurring.prior.to.dissociation,.providing.information.on.the.overall.eficiency.of.
movement..In.nano-.to.microscale.biological.environments,.viscous.forces.dominate.and.
can. impact. motor. forces. and. trajectories.. Processivity. is. a. general. parameter. for. motors.
primarily.functioning.in.transport.roles,.so.not.all.cytoskeletal.motors.are.processive..For.
myosins,.those.that.are.processive,.such.as.myosin.V.or.myosin.VI,.are.typically.dimeric.
in.form..Similar.to.a.human.stride,.asymmetrically.moving.dimeric.heads.of.myosins.pro-
vide.a.constant.source.of.attachment..In.addition,.the.long.strides.of.myosin.V.that.average.
36.nm.are.required.to.obtain.a.linear.trajectory.of.the.motor.along.the.actin.track.that.is.
helical.by.nature.(for.review,.see.Mehta,.2001)..Other.dimeric.myosins.are.nonprocessive..
This. includes. muscle. myosin. II.. As. well,. some. single-headed. myosins,. such. as. myosin.
IX,.employ.an.alternative.mechanism.to.remain.associated.to.the.actin.track.throughout.
ATP.hydrolysis.and.are.surprisingly.processive.(Liao.et.al.,.2010)..Similar.indings.apply.
to.kinesin.and.Klps..The.monomeric.Kif1A.motor.is.processive.(Hirokawa.et.al.,.2009).and.
although.conventional.dimeric.kinesin.is.highly.processive.(Toprak.et.al.,.2009),.this.is.not.
dependent.on.its.dimeric.form.(Xie,.2010)..Processivity.for.conventional.kinesin.appears.to.
be.largely.attributed.to.its.motor.domain,.as.demonstrated.by.generation.of.a.monomeric.
kinesin.that.retains.strong.interactions.with.microtubules.and.processivity..However,.the.
neck.domain.also.plays.a.role.(Romberg.et.al.,.1998)..Those.motors.that.exhibit.limited.pro-
cessivity.generally.contain.specialized.functional.domains.to.enable.alternate.capabilities.
in.non-transport.roles..This.review.focuses.primarily.on.kinesin.and.Klps.in.nanodevice.
applications.. Characteristics. of. processivity. along. with. additional. motor. parameters. for.
kinesin.and.Klps.can.be.found.in.Table.4.2..Information.on.similar.parameters.for.myosins.
can.be.found.in.alternate.reviews.(Krendel.and.Mooseker,.2005;.O'Connell.et.al.,.2007).
4.2.5 Motor Folding as a Means of regulation
Molecular.motors.are.powerful.multifunctional.components.involved.in.numerous.cellular.
processes..As.such,.they.require.regulated.activity.to.optimize.the.timing.and.impact.of.
their.contributions.(Verhey.and.Hammond,.2009)..The.ability.of.kinesin,.and.some.Klps.and.
myosins,.to.fold.back.on.themselves.in.an.inactive.conformation.has.led.to.the.use.of.more.
truncated.forms.in.motility.assays..This.capability.is.discussed.here.as.a.regulatory.tool.
for.nanodevices..Structural.elements.in.conventional.kinesin.display.an.afinity.that.gener-
ates.a.folded.conformation.under.normal.physiologic.conditions..The.conserved.tail.region.
associates.with.the.motor/head,.which.forces.the.associated.light.chain.peptides.of.the.tail.
region.to.be.in.close.proximity.with.the.motor.domain.(for.review.see.Hackney,.2007)..This.
conformation. effectively. nulliies. motor. domain. afinity. with. microtubule. tracks.. It. was.
originally.postulated.that.simple.cargo.attachment.would.sufice.to.initiate.the.transition.
