Biomedical Engineering Reference
In-Depth Information
Conventional.kinesin.has.been.extensively.characterized.for.its.role.in.vesicle.transport.
(Hirokawa.et.al.,.2009)..Unlike.most.Klp.families,.its.structure.contains.protein.heavy.and.
light.chains.in.the.form.of.a.heterotetramer..Its.motor.domain.is.located.at.the.N-terminus.
of.the.polypeptide.and.is.a.component.of.the.heavy.chain.along.with.the.adjacent.neck,.
and. more. distal. stalk. that. contains. a. hinge. and. coiled-coil. region. (Vale. and. Fletterick,.
1997)..The.roughly.45.kDa.motor.domain.of.kinesin.is.highly.conserved.among.Klps.and.is.
smallest.in.comparison.with.myosin.or.the.multiprotein.microtubule.motor.dynein.(Yang.
et.al.,.1989;.Cope.et.al.,.1996;.Vogel,.2005;.Carter.et.al.,.2011)..The.associated.light.chains.in.
kinesin.are.bound.to.the.opposite.end.of.its.stalk.region..These.light.chains.function.in.
cargo. attachment. for. transport.. Kinesin. belongs. to. the. kinesin-1. family. of. microtubule.
motors.and,.like.its.Klp.relatives.in.kinesin.families.2-14,.it.shares.similarities.in.addition.
to.high.degrees.of.specialization.
The. location. of. the. motor. domain. within. the. polypeptide. has. been. found. to. correlate.
closely. with. directionality,. that. is,. N-terminal. for. plus-end-directed. motor. proteins. or.
C-terminal.as.in.the.case.of.kinesin-14.Klps..Distinct.neck.domains.are.also.present..The.
neck.can.be.divided.into.two.segments,.a.linker.region.and.coiled-coil.segment..The.linker.
region. can. act. as. a. spring-like. element. contracting. or. extending. to. produce. force,. while.
the.coiled-coil.region.functions.in.processivity.(Vale.and.Fletterick,.1997)..In.contrast,.the.
tail. and. stalk. domains. of. kinesins. and. Klps. remain. to. be. fully. characterized,. and. it. is.
these.critical.domains.that.appear.to.add.diversity.in.motor.localization,.cargo.association,.
and.other.functions..Kinesin.and.Klp.molecular.motors.are.not.only.being.harnessed.for.
applications. in. biosynthetic. nanorobotic. systems. (Table. 4.1). but. also. are. expected. to. be.
useful.reagents.in.future.therapeutic.applications.(Cohen.et.al.,.2005;.Fischer.et.al.,.2009;.
Agarwal.and.Hess,.2010).
4.2.4 Force generation and Processivity of Myosins, Kinesin, and Klps
ATP.binding.by.motor.proteins.and.hydrolysis.through.a.stepwise.cycle.of.ATP-based.
states. regulates. motor. protein. interactions. with. the. cytoskeleton. and. drives. conforma-
tional.changes.for.motility.and.force.production.(Mikhailenko.et.al.,.2010)..In.muscle.cells,.
chemical. energy. stored. in. ATP. is. converted. to. mechanical. energy. of. the. myosin. head.
to.generate.translational.sliding.of.microilaments..The.myosin.ATP-cycle.mechanism.is.
essentially.as.follows:.a.single.ATP.molecule.binds.to.the.appropriate.catalytic.site.of.the.
motor.(head).domain..ATP.binding.causes.the.myosin.head.to.be.released.from.the.actin.
microilament.and.to.rise.perpendicularly..The.subsequent.hydrolysis.of.ATP.to.generate.
ADP.plus.Pi.provides.energy..The.head.retracts.backward,.and.the.sudden.release.of.Pi.
provides. a. kick. to. generate. the. power. or. working. stroke.. The. power. stroke. sweeps. the.
myosin.head.against.an.actin.subunit.within.the.microilament.and.causes.a.net.forward.
motion. of. the. entire. thin. ilament.. The. release. of. ADP. is. the. rate-determining. step. for.
myosin.motility,.and.upon.its.release,.the.head.domain.swings.back.to.the.nucleotide-free.
state.where.it.is.available.to.re-enter.the.ATP-cycle.(for.review,.see.O'Connell.et.al.,.2007;.
De. La. Cruz. and. Olivares,. 2009).. In. muscles,. it. is. the. action. of. vast. networks. of. myosin.
heads.along.thick.ilaments.and.over.thin.microilaments.that.produces.the.very.notice-
able.macroscale.muscle.contraction.we.observe.when.we.lex.our.muscles.
In.contrast.to.the.ATP-cycle.of.myosins,.during.kinesin.motility,.the.binding.of.ATP.
promotes. microtubule. association. (for. review,. see. Howard,. 1996;. Schief. and. Howard,.
2001)..The.binding.of.kinesins.to.microtubules.in.the.ATP-bound.state.and.its.subsequent.
hydrolysis. to. ADP. plus. Pi. allows. release. of. the. kinesin. motor. head,. repositioning. of.
the. neck,. and. ultimately. forward. movement. (Rice. et. al.,. 1999;. Hirose. et. al.,. 2008;.
