Biomedical Engineering Reference
In-Depth Information
(b)
(+)
(-)
(+)
(-)
(a)
(c)
Figure 4.1
(See companion CD for color igure.)
Molecular.motors.of.the.cytoskeleton..(a).Microtubules.(blue.and.white).
exhibit. polarity. and. accommodate. cargo-bound. conventional. kinesin. (top,. black),. homotetrameric. kinesin-5.
(middle-left,. red),. and. kinesin-14. (bottom,. purple).. Dynein. (middle-right,. green). binds. to. microtubules. via.
two.microtubule-binding.domains.that.attach.two.AAA+.catalytic.motor.domains.(green)..Intermediate.and.
light.chains.extend.upward.from.these.catalytic.domains.and.bind.cargo.(blue)..(b).Processive.myosin.V.(not.
attached.to.cargo).moves.along.branched.actin.ilaments.(red)..The.distance.between.the.myosin.V.actin-bound.
heads.is.~35.nm...This.equates.to.a.~74.nm.step.size.as.one.myosin.arm.swings.around.the.pivot.point.of.the.
other.during.walking.and.contrasts.with.the.average.8.nm.steps.exhibited.by.motile.kinesin..(c).Nonprocessive,.
dimeric.myosin.II.heads.extrude.from.myosin.thick.ilaments.and.harness.ATP.hydrolysis.to.push.unbranched.
actin.thin.ilaments.along.
ubiquitous,.not.all.species.or.cell.types.contain.the.same.myosin.family.or.member.(Sellers.
and.Goodson,.1995;.Hodge.et.al.,.2000;.Gillespi.et.al.,.2001)..Conserved.structural.elements.
present.in.myosins.allow.for.their.identiication,.although.variability.in.protein.conforma-
tion.and.function.are.known.to.exist.even.within.one.family.
Over. 40. years. of. research,. including. more. recent. technical. single-molecule. luores-
cence.(Funatsu.et.al.,.1995,.and.references.therein),.high-speed.atomic.force.microscopy.
video.studies.(Kodera.et.al.,.2010),.and.total.internal.relection.luorescence.or.total.inter-
nal.luorescence-based.dark.ield.microscopy.with.myosin.conjugated.to.quantum.dots.
or.gold.nanoparticles,.respectively.(Nishikawa.et.al.,.2010),.have.revealed.highly.detailed.
biochemical.and.structural.insights.into.the.myosin.mechanism..Myosins.are.composed.
of. protein. heavy. and. light. chains.. The. heavy. chain. includes. critical. motor,. hinge,. and.
tail. domains. (Vogel,. 2005).. The. 80.kDa. catalytic. motor. domain. is. responsible. for. actin.
binding,.enzymatic.ATP.hydrolysis,.and.force.generation.(Cope.et.al.,.1996)..Referred.to.
as.the.“head,”.this.domain.is.analogous.to.a.“foot”.as.it.steps.along.actin.tracks..Tail.and.
hinge.domains.are.extended.coiled-coil.structures.and.constitute.a.lever.arm..Myosins.
use.ATP.binding.to.release.the.head.from.actin.microilaments.and.mechanical.energy.
transfer. between. the. two. heads. to. generate. conformational. changes. needed. for. motil-
ity.. The. release. of. phosphate. upon. ATP. hydrolysis. leads. to. a. powerstroke. and. swing-
ing.of.the.lever.arm.via.a.proposed.hand-over-hand.model..In.muscle.contraction,.it.is.
the. lever. arm. that. makes. it. possible. for. myosin. to. generate. a. power. stroke. to. provide.
