Molecular Motors - The Nanobiotechnology - page 89

to.an.active.conformation.(Coy.et.al.,.1999)..However,.more.recent.indings.suggest.an.alter-
native.model..In. D. melanogaster ,.cargo.attachment.must.be.paired.to.the.activity.of.other.
proteins.to.promote.activation.(Blasius.et.al.,.2007)..Requiring.multiple.events.to.activate.a.
functional.conformation.makes.sense.in.terms.of.autoinhibitory.or.poised.mechanisms.
Members.of.the.myosin.superfamily.also.self-regulate.by.defaulting.to.a.folded,.compact.
conformation..For.example,.when.both.muscular.and.non-muscular.myosin.II.motors.are.
in.monomeric.form.(as.opposed.to.being.arranged.as.thick.ilaments),.there.is.a.close.pack-
ing.conformation..The.two.heads.pack.together.along.with.a.tri-segment.folding.of.the.tail.
that.is.associated.primarily.with.a.single.head.(Jung,.2011)..In.smooth.muscle.myosin,.the.
transition.to.a.functional.open.form.is.aided.by.the.phosphorylation.of.light.chains,.thus.
the.recognition.as. regulatory .light.chains.(Sweeney,.1998)..Unconventional.processive.myo-
sin.V.also.employs.folding.as.a.regulatory.mechanism..Truncation.of.myosin.V.constructs.
removes.this.capability..In.addition.to.folding,.other.factors.may.regulate.motor.function..
Myosin.V.motility.and.function.are.also.highly.regulated.by.Ca 2+ .ions.in.association.with.
the.calcium-modulated.protein,.calmodulin.(Kremenstov.et.al.,.2004)..In.choosing.motors.
for. incorporation. into. nanodevices,. evaluation. of. the. optimal. motor. must. be. based. not.
only.on.functional.parameters.and.device.needs.but.also.its.regulatory.framework.
4.2.6 Dynein: A Multiprotein Microtubule Motor
Dynein.is.a.massive.microtubule.motor.protein.that.dwarfs.myosin.or.kinesin.family.motor.
proteins.(Gibbons.et.al.,.1994;.Carter.et.al.,.2011;.for.review,.see.Vogel,.2005)..An.important.
difference.between.the.catalytic.core.of.dynein.and.those.of.myosins.and.kinesins.is.that.
in.dynein.this.domain.is.distant.from.its.microtubule.track..A.15.nm.stalk.on.each.of.two.
massive.ring-like.domains.that.contains.the.catalytic.core.acts.as.an.extended.tether.to.fulill.
the. microtubule-binding. domain. (MTBD). role. and. to. help. guide. the. motor. directionally.
to. microtubule. minus. ends. (Carter. et. al.,. 2008;. Tanenbaum. et. al.,. 2011).. The. catalytic. core.
structures.from.which.the.stalks.extend.are.known.as.AAA+.rings..Four.AAA+.domains.
of. a. single. ring. are. able. to. bind. and. hydrolyze. ATP.. In. cytoplasmic. dynein,. two. of. these.
rings.are.present.and.together.compose.the.motor.region..The.AAA+.rings.along.with.the.
two.stalks.and.two.MTBDs.make.up.dynein's.heavy.chain.(Carter.et.al.,.2008,.2011),.while.
intermediate.and.light.chain.protein.complexes.function.in.the.binding.of.cargo..The.recent.
crystal. structure. of. dynein. reveals. that. there. are. critical. residues. required. to. accomplish.
cargo. binding. (Hall. et. al.,. 2010).. While. dyneins. across. species. retain. these. conserved.
residues,.they.also.exhibit.evolutionary.adaptation.to.increase.the.lexibility.of.the.structure..
Functions.of.dynein.are.extensive.and.include.mitotic.spindle.regulation.and.orientation,.
mitotic.checkpoints,.and.cytoplasmic.roles.in.the.transport.of.vesicles.and.others.cargos.(for.
review,.see.Ahringer,.2003;.Bader.and.Vaughan,.2010;.Allan,.2011)..This.large.motor.protein.
is.also.critical.to.the.operation.of.mobility.tools.such.as.cilia.and.lagella.where.it.localizes.to.
the.cellular.cortex.in.these.cells.(for.review,.see.Walczak.and.Nelson,.1994)..As.well,.it.serves.
an.important.role.in.neuronal.function.in.more.complex.eukaryotes.along.with.kinesins.and.
myosins..A.new.role.for.dynein.in.budding.yeast.is.the.sliding.of.microtubules.(Moore.et.al.,.
2009).. Despite. these. impressive. capabilities,. dynein. is. not. ubiquitous. among. eukaryotes.
(Lawrence.et.al.,.2001)..In.these.organisms,.Klps.are.expected.to.have.replaced.key.roles.
4.2.7 Non-Tracking Cellular Molecular Motors
A. review. of. cellular. molecular. motors. would. not. be. complete. without. some. discussion.
of.motors.that.perform.absolutely.vital.functions.to.cells.but.which.are.not.motile.along.