Environmental Engineering Reference
In-Depth Information
BiochemistryofCopperTransport
Types of Copper Transport Proteins
Copper.uptake.and.distribution.is.tightly.regulated.because.free.copper.ions.
are. very. toxic,. even. at. low. levels.. The. presence. of. free. copper. ions. (Cu(I).
or.Cu(II)).in.the.cell.can.cause.autooxidation.of.proteins,.lipids,.and.nucleic.
acids. (O'Halloran. and. Culotta. 2000).. It. is. speculated. that. intracellular. free.
copper.concentrations.are.very.low.because.of.the.binding.capacity.of.pro-
teins. that. can. sequester. and. trafic. these. metal. ions. (Rae. et. al.. 1999).. The.
three.major.categories.of.copper.homeostasis.proteins.are.membrane.trans-
porters,.copper.chaperones,.and.metallothioneins.
Currently,. it. is. unknown. which. form. of. copper. is. generally. taken. up. by.
different.organisms;.however,.experimental.data.in.yeast.suggest.copper.is.
imported. as. Cu(I). (Dancis. et. al.. 1994,. Knight. et. al.. 1996,. Puig. et. al.. 2002)..
Some. organisms. such. as. yeast. contain. metalloreductases. on. the. plasma.
membrane.to.reduce.Cu(II).to.Cu(I).extracellularly.before.transport.(Hassett.
and. Kosman. 1995,. Georgatsou. et. al.. 1997).. Once. copper. has. been. reduced,.
there. are. several. different. types. of. transporters. that. can. transport. Cu(I).
across. cell. membranes.. One. common. type. of. transporters. is. the. copper.
transporter.family.(Ctr).irst.discovered.in.plants.but.most.studied.in.yeast..
Members.of.this.family.are.predicted.to.have.three.transmembrane.domains.
and.are.rich.in.Met.and.Cys/His.motifs.(Figure.13.1A).(Harris.2000,.Puig.and.
Thiele.2002,.Dumay.et.al..2006)..Depending.on.the.organism,.the.Met.motifs.
can. vary. between. MxM,. MxxM,. and. MxMxM,. but. are. generally. found. as.
repeat.motifs.at.the.amino.terminus..Sequences.that.are.rich.in.cysteine.and.
histidine. can. be. found. at. the. carboxy. terminus. which. is. thought. to. be. in.
the.cytosol.(Puig.and.Thiele.2002,.Dumay.et.al..2006)..In.addition.to.yeast,.
copper. transporters. (Ctr). are. found. in. a. wide. variety. of. eukaryotic. organ-
isms.ranging.from.plants.to.mammals,.including.
Arabidopsis
.(COPT.family).
(Sancenon.et.al..2003).
A. second. group. of. membrane. transporters. is. a. diverse. superfamily. of.
P-type. ATPases. found. in. virtually. every. kind. of. organism.. The. mem-
brane. transporters. that. comprise. this. large. group. are. categorized. by.
their. ion. speciicity. (Axelsen. and. Palmgren. 2001,. Kuhlbrandt. 2004).. The.
heavy-metal-associated. (HMA). family. of. ion. transporters. is. classiied. in.
the. P
1B
-type. ATPased. sub-family.. This. group. is. predicted. to. have. eight.
transmembrane.domains.with.a.large.cytosolic.loop.between.the.sixth.and.
seventh.transmembrane.domain.(Figure.13.1B).(Williams.et.al..2000,.Hall.
and.Williams.2003)..There.is.a.heavy.metal.binding.domain.at.the.amino.
and/or.carboxy.termini.as.well.as.a.CPx.motif.in.the.sixth.transmembrane.
domain.that.is.thought.to.function.in.ion.transduction.(Williams.and.Mills.
2005,.Arguello.et.al..2007)..Another.conserved.sequence.is.DKTGT,.found.
in. the. large. cytosolic. loop,. which. is. the. site. of. phosphorylation.. Once. a.
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