Handling Copper: A Paradigm for the Mechanisms of Metal Ion Homeostasis - Environmental Contamination: Health Risks and Ecological Restoration - page 271

copper.transport.in.the.phloem,.while. MT2a .and. MT3 .sequester.excess.metal.
ions.in.mesophyll.cell.and.root.tips.(Guo.et.al..2003).
Metal-Related Interactions and Specificity
Metal. binding. sequences. generally. include. cysteine. and/or. histidine. resi-
dues. in. the. following. motifs:. CxxC,. CCxSE,. His-rich. (including. Hx. and. H.
repeats),. Cys-rich,. and. Cys/His-rich. (Arnesano. et. al.. 2002,. Arguello. et. al..
2007).. This. is. especially. true. for. P 1B -type. ATPase. transporters,. but. these.
motifs.can.also.be.found.in.copper.chaperones.and.metallothioneins..Several.
protein-protein.interactions.between.these.transporters.and.copper.chaper-
ones.have.been.observed.using.yeast.2-hybrid.assays.as.well.as.biochemical.
metal.transfer.assays.(Huffman.and.O'Halloran.2000,.Tottey.et.al..2002,.van.
Dongen.et.al..2004,.Andres-Colas.et.al..2006)..The.P 1B -type.ATPase.subgroup.
of.transporters.is.further.divided.into.two.different.groups.based.on.the.puta-
tive.heavy.metals.they.are.hypothesized.to.transport..The.irst.group.is.the.
Zn 2+ /Co 2+ /Cd 2+ /Pb 2+ .ion.transporters.and.consists.of.HMA1,.HMA2,.HMA3,.
and. HMA4. in. Arabidopsis ;. while. the. second. group. includes. HMA5,. PAA1.
(HMA6),. RAN1. (HMA7),. and. PAA2. (HMA8). and. is. thought. to. transport.
Cu 2+ /Ag 2+ . ions.(Axelsen. and. Palmgren. 1998,. 2001).. These. two. groups. were.
originally.developed.based.on.sequence.and.phylogenetic.analysis.with.the.
transporters.in.the.Zn.group.containing.histidine.rich.regions.in.the.amino.
and/or. carboxy. termini. areas. of. the. proteins,. whereas. the. transporters. in.
the. Cu. group. have. one. or. two. MxCxxC. heavy. metal. binding. domains. in.
their.amino.terminus.region..There.has.been.a.signiicant.amount.of.experi-
mental. data. that. supports. the. classiication. of. these. two. groups;. however,.
more.recently.there.has.been.some.implication.that.HMA1.could.be.a.copper.
transporter.rather.than.a.Zn.transporter.as.hypothesized.(Seigneurin-Berny.
et.al..2006)..The.protein.sequence.of.HMA1.is.slightly.different.from.HMA2,.
3,.and.4.in.that.the.histidine.rich.region.is.in.the.amino.terminus.and.it.has.a.
rather.short.carboxy.terminus..These.differences.between.the.HMA1.trans-
porter.and.others.in.the.Zn.or.Cu.groups.have.created.much.dispute.over.the.
function.of.this.protein.
Metal.speciicity.seems.to.rely.on.both.positions.of.conserved.amino.acid.
residues.as.well.as.the.conformational.structure.of.each.protein..Recently,.
it.has.been.suggested.that.sequences.within.the.sixth,.seventh,.and.eighth.
transmembrane. domains. in. the. P 1B -type. ATPase. transporters. contrib-
ute. to. metal. speciicity. (Arguello. et. al.. 2007).. Copper. ions. have. an. afin-
ity. to. bind. to. sulfur. or. nitrogen. ligands. in. histidine,. methionine,. and/or.
cysteine. amino. acids.. This. is. true. in. plastocyanin. where. copper. is. bound.
to. two. nitrogen. ligands. in. two. histidine. residues. and. two. sulfur. ligands,.
one. in. each. cysteine. and. methionine. (Figure. 13.3A). (Bhattacharya. 2005)..
In.copper.traficking.proteins.that.have.a.conserved.MxCxxC.heavy.metal.
binding.domain,.copper.coordination.is.theorized.to.be.isolated.to.two.sul-
fur. ligands. in. the. two. cysteine. residues. (Figure. 13.3B). (Rosenzweig. and.