MetallothioneinsMetallothioneins

The real stateThe real state--ofof--thethe--artartThe real stateThe real state--ofof--thethe--artart

Òscar PalaciosÒscar PalaciosDept QuímicaDept QuímicaDept. QuímicaDept. QuímicaUniversitat Autònoma de BarcelonaUniversitat Autònoma de Barcelona

MetallothioneinsMetallothioneins ((MTsMTs))MetallothioneinsMetallothioneins ((MTsMTs)) Ubiquitous proteins: animals plants Ubiquitous proteins: animals, plants,

prokaryotes Small metalloproteins (40-100 aa)Small metalloproteins (40 100 aa) High sequence heterogeneity General absence of aromatic amino acids Cysteine-rich (~ 30 %) High metal-chelating capacity (thiol groups)g g p y ( g p ) No 3D structure of the apo form

structuration related with the formation of metal clusters

Biological role: metal homeostasis and detoxification, radical scavenging, …

HistoricalHistorical overviewoverviewHistoricalHistorical overviewoverview Scifinder: ~140000 results ISI Web of Knowledge: ~13000 results (papers, books and

reviews) PubMed: ~10000 results

600

700

MTI

MTII

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catiom

s

300

400

Num

ber o

f pub

lic

MTIII MTIV

100

200MTIII

0

1970

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Years

HistoricalHistorical overviewoverviewHistoricalHistorical overviewoverview Fields of interest on MTs: a clear Fields of interest on MTs: a clear

change in tendency

BIOL TRACEENVIRON. 

2007‐2011COMP. BIOCHEM. PHYSIOL. C‐ PROC NAT

1990‐1995

BIOL. TRACE ELEMENT 

RES.BIOMETALS

ENVIRON

CHEMOSPHERE

POLLUTIONJOURNAL OF BIOLOGICAL CHEMISTRY

PHARMACOL. TOXICOL. 

ENDOCRINOL.TOXICOL. LETTERS

PROC. NAT. ACAD.  

SCIENCES USA

ECOTOXICOL. ENVIRON. SAFETY

COMP. BIOCHEM. 

ARCH. ENVIRON. CONTAM. TOXICOL.

ENVIRON. TOXICOL. CHEM.METH. ENZYM.

BIOCHEM. J.

TOXICOLOGY

PHYSIOL. C‐TOXICOL. 

PHARMACOL.

AQUATIC TOXICOL.

TOXICOL. APPL. PHARMACOL.

BIOL. TRACE ELEMENT RES.

MOL. CEL. BIOL.

TOXICOL. APPL. PHARMACOL.

Accepted features (end of the Accepted features (end of the

Classification of MTs in three classes90’s)90’s) Classification of MTs in three classes Coordination only by Cys residues Native complexes = metal-thiolates (in vivo Native complexes = metal-thiolates (in vivo

= in vitro) Ag(I) as model of Cu(I) and Cd(II) as model Ag(I) as model of Cu(I) and Cd(II) as model

of Zn(II) in Cu-MT and Zn-MT Very fast metal-substitution reactionsVery fast metal substitution reactions The amounts of metal added accounts for the

metal-MT stoichiometry, until saturation of the y,protein

Higher organisms: bidominial Zn-MTsg g Lower organisms: monodominial Cu-MTs

Zn7-MT1Cd7-MT1(mamals)

Cu8-Cup1 (yeast)

Inflexion point in the MTs fieldInflexion point in the MTs fieldInflexion point in the MTs fieldInflexion point in the MTs field

R bi t th iRecombinant synthesisof MTs

MTs of manyMTs of many organisms High purity

and high t

Mutant forms

amounts

First steps in the MTs fieldFirst steps in the MTs fieldFirst steps in the MTs fieldFirst steps in the MTs field

Pilar & Roser Gonzalez-Duarte(UAB) (UB)(UAB) (UB)

Mercè Capdevila & Sílvia Atrian(UAB) (UB)

E. coli culturesGenetic engineering

Metal-MT complexes

Chemical characterization

Metal-binding features

Sequence / function relationship

Classification, Evolutionary differentiation, Function

Experimental approachExperimental approachExperimental approachExperimental approach

In vivo Recombinant MT synthesis (wild type, domains or mutants)

Cd(II)  Cu(II) Zn(II)  Supplemented media

Acidification & Cd(II) Cu(I)

CdII‐MT CuI‐MTZnII‐MT

reneutralization( )

titration( )

titration

CdII MT CuI MT

In vitroCdII‐MT CuI‐MT

Experimental strategiesExperimental strategiesExperimental strategiesExperimental strategies

Atomic Emission

CD & UV-Vis- Metal-MT folding degree- Chromophores

Mass Spectrometry (ESI-MS)- Stoichiometry

Spectrometry (ICP-AES)- Protein concentration- Global metal-MT Stoichiometry

I t l Tit ti

- Stoichiometry- Molecular distribution of the existing metal-MT complexes

Isotermal Titration Calorimetry (ITC)- Thermodinamics

00

6

-4

-2

0

Data: A120509CUP1P_NDHModel: OneSitesChi^2/DoF = 3.386E4N 3.96 ±0.0698K 3.15E5 ±3.93E4H -7731 ±200 5/m

ole

of in

ject

ant

6

-4

-2

0

Data: A120509CUP1P_NDHModel: OneSitesChi^2/DoF = 3.386E4N 3.96 ±0.0698K 3.15E5 ±3.93E4H -7731 ±200 5/m

ole

of in

ject

ant

0 2 4 6 8 10 12-8

-6 H 7731 ±200.5S 0.855

Molar Ratio

kcal

/

0 2 4 6 8 10 12-8

-6 H 7731 ±200.5S 0.855

Molar Ratio

kcal

/

ProchordateProchordate

MT1 to MT4Villarreal et al., FEBS J., (2006), 273, 523

&

Artells et al., Metallomics, (2013)Tio et al., JBC, (2004), 279, 24403Bofill et al., JBIC, (2001), 6, 405Cols et al., Prot Engng., (1999), 12, 265

ProchordateProchordate

Valls et al., JBC, (2001), 276, 32835

Pagani et al., JIB, (2012), 117, 306

......

Guirola et al., PLos ONE, (2012), 7, e43299

&Domenech et al., JBIC, (2007), 12, 867Domenech et al., Biochimie, (2006), 88, 583

Tomás et al., FEBS OpenBio (2013)

Pérez-Rafael, ZAAC, (2013) Pérez-Rafael, JIB, (2012), 108 Palacios et al BMC (2011) 9:4

CeMT1 & CeMT2

Ding et al., Cell Host & Microbe (2013)C.neoformans

Orihuela et al., JBIC, (2008), 13, 801

Palacios et al., BMC, (2011), 9:4Höckner et al., Biometals, (2011), 24, 1079Pérez-Rafael, Metallomics, (2012), 4, 342

Egli et al., Genes to Cells, (2006), 11, 647Domenech et al., FEBS Lett., (2003), 533, 72Valls et al., FEBS Lett., (2000), 467, 189

CUP1 Crs5

Domenech et al., BBA, (2008), 1784, 693Bofill et al., FEBS J, (2009), 276, 7040

Pagani et al., Mol. Microbiol., (2007), 63, 256

Orihuela et al., Chem. Eur. J., (2010), 16, 12363

Diverse MTs discovered and Diverse MTs discovered and studiedstudied

H MT1Human MT1MDPNCSCAAGVSCTCAGSCKCKECKCTSCKKSCCSCCPVGCSKCAQGCVCKGASEKCSCCD

C.elegans MT1MACKCDCKNKQCKCGDKCECSGDKCCEKYCCEEASEKKCCPAGCKGDCKCANCHCAEQKQCGDKTHQHQGTAAAH

MPCPCGSGCKCASQATKGSCNCGSDCKCGGDKKSACGCSE

D.melanogaster MTN

QsMT, plant MTMSCCGGNCGCGTGCKCGSGCGGCKMFPDISSEKTTTETLIVGVAPQKTHFEGSEMGVGAENGCKCGSNCTCDPCNCK

TpyMT1, Tetrahymena MT

MGVGAENGCKCGSNCTCDPCNCK

MDKVNNNCCCGENAKPCCTDPNSGCCCVSETNNCCKSDKKECCTGTGEGCKWTGCKCCQPAKSGCCCGDKAKACCTDPNSGCCCSSKTNKCCDSTNKTECKTCECCK

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes Cooperative processes Cooperative processes

Zn7-MT1 + 2 Cd(II)

St i hi t t f t l dd d Stoichiometry vs. amount of metal added

Ag(I) equivalents added

Ag2Zn3-MT1Ag1Zn3-MT1

XXXXZn4-MT111109876543210

X major species minor species

XXAg6Zn1-MT1Ag4Zn2-MT1

XXXAg3Zn2-MT1Ag2Zn3 MT1

XAg11-MT1XXXXAg9-MT1

O. Palacios et al., JBIC, (2003) 8: 831-842

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes Speed of metal substitution reactions Speed of metal substitution reactions

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes The role of Zn(II) as a structural ion The role of Zn(II) as a structural ion

CeMT1

MeMT-10-IV

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes Ag(I) as a model for Cu(I) in Cu-MT? Ag(I) as a model for Cu(I) in Cu-MT?

In mammalian MT1 only in the presence of Zn(II)(O. Palacios et al., JBIC (2003) 8: 831-842)Ag7-Cup1 different of Cu7- and Cu8-Cup1(C.W. Peterson et al., FEBS Lett (1996) 379:58-93)

Cd(II) d l f Z (II) Z MT? Cd(II) as a model for Zn(II) en Zn-MT?

S. cerevisiae Cup1Cd Cd S Cd SZn4 > Zn3, Zn5Cd5 >> Cd6S1 > Cd7S1

(Orihuela et al., Chem-Eur J (2010) 16:12363-12372)

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes M-MT species ¿in vivo = in vitro? M-MT species ¿in vivo = in vitro?

MeMTMeMT--1010--IVIV

The binding role of His residuesWheatWheatZnZn44--EEcc--11

CianobacteriaCianobacteriaZnZn44--SmtA SmtA

C. A. Blindauer, Proc Natl Acad Sci USA (2001) 98:9593-9598 E.A. Peroza, J Mol Biol (2009) 387:207-218

CyanobacteriaCyanobacteriaCyanobacteriaCyanobacteriaZnZn44--SmtA SmtA

WheatWheatZnZn EE 11ZnZn44--EEcc--11

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes A sulfide surprise: S2- ions involved in metal

M. Capdevila et al., Angew. Chem. Int. Ed., (2005), 44 4618

A sulfide surprise: S ions involved in metal binding44, 4618

Cd-SCys Cd-S2-

TEM

Crystallites

D.R. Winge et al., Metallothioneins, VCH, 1992

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes Evidence of the presence of S2- in native Evidence of the presence of S in native

complexes1st step of purification

Anionic Exchange Chromatography

1 step of purification

Cadmium-resistant S. cerevisiae strain 301N supplemented with 500 μM CdSO4 Size Exclusion Chromatography (Sephadex G-75)Size Exclusion Chromatography (Sephadex G 75)

ChromatogramCadmium

Purification of the cadmium rich fractions by two different procedures

FPLC size l i

Cd

(ppm

) exclusion

time (min)

Sulfide contribution at 280 nm

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes Participation of Cl- ions in metal binding Participation of Cl ions in metal binding Importance of the degree of oxigenation in the

E. coli cultures for the formation of Cu-MTE. coli cultures for the formation of Cu MT species

Importance of the purity of Zn-MT samples in p p y pmetal-replacement reactions

Fine tuning the classification of Fine tuning the classification of MTsMTs

• 1st Kägi’s classification: Mammalian-homology3 classes:

Class I: Homology to mammalian MT1Class II: Non-homology to mammalian MT1 (neither among them! )

1 Kägi s classification: Mammalian homology criteria

gy ( g )Class III: Phytochelatins (non gene-encoded peptides)

• 2nd Kägi’s classification: Taxonomic criteriaAn MT family for each taxon

• Zn/Cd-thioneins vs. Cu-thioneins Metal-MT complex features Protein sequence similarity analysis Gene inducibility criteria

Zinc-Thionein vs. copper-Thionein character of MTsValls et al JBC (2001) 276 32835

zinc (or cadmium) copper

Valls et al., JBC, (2001), 276, 32835

- heteronuclear Zn/Cd + Cu complexes- low folding and high oxidation

-fully-metalated metal complexes- high folding degree low oxidation low folding and high oxidation

degree- variable Zn/Cd, Cu content

high folding degree, low oxidation- one prevalent complex (with the expectable stoichiometry) and other minor forms

Zn/Cd-Th

- mixture of Zn (or Cd) species (different stoichiometries)stoichiometries)- variable folding and oxidation degree- two or more equally-prevalent

- fully-metalated copper complexes- high folding degree, low oxidation- one prevalent complex (with the expectable stoichiometry) and otherCu-Th stoichiometries

- requirement of additional ligands (for Cd2+), chloride, sulfide

expectable stoichiometry) and other minor forms

Cu-Th

New classification proposalNew classification proposalNew classification proposalNew classification proposalMouseMouse Chicken MT1Chicken MT1

Cu Zn ckMT1Cu-Zn MT1

Zn-thionein

Cu-Zn ckMT1Zn-thionein

But better for copper-Cu-Cu MT4

Cu-thionein

Tio et al., JBC, (2004), 279, 24403

ppcoordination than mMT1 !!!

Tio et al., JBC, (2004), 279, 24403

Lobster MTHLobster MTHVillarreal et al., FEBS J., (2006), 273, 5

MtnA (MTN)MtnB (MTO)

Fruit FlyFruit Fly

Cu-thioneins

(MTO)MtnCMtnD

Zn-Zn Zn-thionein Cu thioneins

Egli et al., Genes to Cells, (2006), 11, 6

Zn Zn Zn thionein

Valls et al., JBC, (2001), 276, 32835

Fine tuning of the classification of Fine tuning of the classification of MTMT

Bofill et al., Metallomics (2009), 1, 229Capdevila et al., (2010) Bioinorg Chem Appl 1-6 (doi:

Genuine Zn-thioneinsCeMT1 C. elegans p , ( ) g pp (

10.1155/2010/541829)Ce C e ega s

MeMT M. edulis

MT1 M. musculus

HpCdMT H pomatia 1 Presence/absence of ZnII in theHpCdMT H. pomatia

TpyMT1 T. pyriformis

SpMTA S. purpuratus

CkMT G ll

1. Presence/absence of ZnII in the biosynthesized Cu-MT species

2 Number of CuI equivalentsCkMT G. gallus

MTH H. americanus

CeMT2 C. elegans

2. Number of CuI equivalents (Cys/Cu ratio) required to in vitro reproduce the biosynthesized Cu-MT species

Crs5 S. cerevisiae

MT4 M. musculus

QsMT Q. suber

Cu MT species

3. Presence/absence of S2- and/or ZnII in the biosynthesized Cd-MT species

HpCuMT H. pomatia

MtnA D. melanogaster

MtnB D. melanogaster

y p

4. Reluctance to in vitro Zn/Cdsubstitution (lack of isostructurality

Cup1 S. cerevisiae

Genuine Cu-thioneins

between the Zn-MT and Cd-MT forms)

New insights into the features of New insights into the features of the metalthe metal--MT complexesMT complexes Effect of the non-binding amino acids

Mammalian Mammalian isoformsisoforms::

Effect of the non-binding amino acids

MT 4 MDPGECTCMSGGICICGDNCKCTTCSCKTCRKSCCPCCPPGCAKCARGCICKGGSDKCSCCP MT 1 MDP NCSCSTGGSCTCTSSCACKNCKCTSCKKSCCSCCPVGCSKCAQGCVCKGAADKCTCCA domain domain

Zn7-MT1Cu10-MT4

domain domain

HpCuMT MGRGKNCGGACNSNPCSCGNDCKCGAGCNCDRCSSCHCSNDDCKCGSQCTGSGSCKCGSACGCK

Snail Snail isoformsisoforms::HpCuMT MGRGKNCGGACNSNPCSCGNDCKCGAGCNCDRCSSCHCSNDDCKCGSQCTGSGSCKCGSACGCKHpCdMT MGKGKGEKCTSACRSEPCQCGSKCQCGEGCTCAACKTCNCTSDGCKCGKECTGPDSCKCGSSCSCK

Native: Cu12-HpCuMT & Cd6-HpCdMT (Palacios et al., (2011) BMC Biol 9:1-20 ) (Dallinger et al., Nature 1997)

CaCdMT MSGKGKGEKCTAACRNEPCQCGSKCQCGEGCTCAACKTCNCTSDGCKCGKECTGPDSCKCGSSCGCK CaCdCuMT MSGKG--SACAGSCNSNPCSCGDDCKCGAGCSCAQCYSCQCNNDTCKCGSQCSTSGSCKCGS-CGCK CaCuMT MSGRG QNCGGACNSNPCNCGNDCNCGTGCNCDQCSARHCSNDDCKCGSQCTRSGSCKCGNACGCKCaCuMT MSGRG--QNCGGACNSNPCNCGNDCNCGTGCNCDQCSARHCSNDDCKCGSQCTRSGSCKCGNACGCK

MammalianMammalian MetallothioneinsMetallothioneins((mMTsmMTs))MT1 MDPN-CSCSTGGSCTCTSSCACKNCKCTSCKKSCCSCCPVGCSKCAQGCVCKGA------ADKCTCCA 61

MT2 MDPN-CSCASDGSCSCAGACKCKQCKCTSCKKSCCSCCPVGCAKCSQGCICKEA------SDKCSCCA 61 MT4 MDPGECTCMSGGICICGDNCKCTTCSCKTCRKSCCPCCPPGCAKCARGCICKGG------SDKCSCCP 62

((mMTsmMTs))

MT3 MDPETCPCPTGGSCTCSDKCKCKGCKCTNCKKSCCSCCPAGCEKCAKDCVCKGEEGAKAEAEKCSCCQ 68

domain domain

Cu ZnMT4MT4MT3MT3 MT2MT2MT1MT1

MammalianMammalian MetallothioneinsMetallothioneins(( MTMT ))

Zn Cd Cu (≈ O2) Cu ( O2)

MT2 2

3

4

4x10Intens. 0 Cd(II)

Zn7

0 0

0.5

1.0

1.5

2.0

2.5

5x10Intens.

Cd7A

Cd7S2

500

1000

1500

2000

Intens. 15 Cd(II)

Zn1Cd7 

Cd7

Zn1Cd6

0.00

0.25

0.50

0.75

1.00

1.25

5x10 Intens.

6600 6700 6800 6900 7000 7100 m/z

M10

M11

M7M9

M8

M12

M13

0

1

2

35x10

Intens.

6200 6400 6600 6800 7000 m/z

Cu10

Cu8

Cu4

Cu6

apo-MT

M7- to M13- composed of:

((mMTsmMTs))MT2

(Metallomics, 2013) 0

1

2

Zn7-MT2

0.06800 6900 7000 7100 7200 m/z 0

1660 1680 1700 1720 1740 1760 1780 m/z Cd7-MT2 Zn7-MT2

+ 15 Cd(II) eq (reluctance)

M7- to M13- composed of:ZnnCu10- ZnnCu6- ZnnCu8-

ZnnCu4-MT2

----------

Zn7 Cu11

MT1 (JBIC 2001)

(Talanta 2002)

Cd7-MT1 Zn7-MT1 + 9 Cd(II) eq ( l t )

Z C MT1Zn7-MT1 (reluctance) Zn3Cu7-MT1

Major Cu11-MT1

MT4 (JBC, 2004)

(Exp Biol MedM8- & M10- with major

Zn3Cu7-MT4

Zn7

(Exp. Biol. Med., 2006)

Zn7-MT4

Zn,Cd-MT4 + Cd-S2--MT4

Zn3Cu7 MT4

Major Cu10-MT4

3

5x10Intens.

Zn7 Zn-MT3

0.8

1.0

4x10Intens.

Cd7

0.6 

0.8 

1.0 

5x10Intens.

M10

M11

pH 7.0A

3

4

5

5x10Intens.

Cu6

Cu10pH 2.4B

6

4x10Intens.

Cu10C

MT3 (submitted)

0

1

2

7400 7500 7600 7700 7800 7900 8000 8100 m/z

Zn5

Zn6

Zn7- > Zn6- > Zn5-MT3

0.0

0.2

0.4

0.6

7850 7900 7950 8000 8050 8100 m/z

Cd7S2

Cd8

Cd7- > Cd7S2- > Cd6-MT3

0.0 

0.2 

0.4 

7500 7600 7700 7800 7900 8000 m/z

M11

M12

M9

0

1

2

7300 7400 7500 7600 7700 7800 m/z

Cu4

Cu8 Cu11

Major M10- composed of: Zn4Cu6-

Cu10-MT3 0

2

4

7650 7700 7750 7800 7850 7900 7950 8000 m/z

Cu11

Cu12

Cu13

Major Cu10-MT3

Metal specificity comes from the MT primary structure but neither Metal specificity comes from the MT primary structure but neither from its Cys content or position nor the metal ion availabilityfrom its Cys content or position nor the metal ion availability

Reactivity of ZnReactivity of Zn--mMTmMT complexes with complexes with PbPb2+2+

MT2MT2

MT1MT1

MT3MT3

MT3MT3 Cup1Cup1pp

ZnZn‐‐mMT + 10 PbmMT + 10 Pb2+2+Reactivity of ZnReactivity of Zn--mMTmMT complexes with complexes with PbPb2+2+

MT1 MT2 MT3 MT4

ZnZn‐‐mMT + 10 PbmMT + 10 PbPbPb

A562nmOrihuela et al., Chem. Commun, (2011), 47, 12155Iron release from Iron release from ferritinferritin by Znby Zn--MT complexesMT complexes

Zn-MT1 : 55.6%

Zn-MT2 : 23.9%3 9%

Zn-MT3 : 59.5%time(h)( )

  (a)  (b) 

Zn7 Zn7

MT2MT2

MT1 

Zn6

Zn5Zn4

Zn3Zn2 

MT2 

Zn7 Zn7

   

Zn7 Zn7

Z MT3MT3MT3 

   

Zn6

Zn5Zn6

Zn5

Zn4Zn3

Zn2

MT3MT3

Metallothioneins: where are Metallothioneins: where are they?they?

Metallicthiolates Metalloproteins

Metallothioneins

Now we can say thatNow we can say thatNow we can say that …Now we can say that … Ag(I) andAg(I) and CdCd(II) cannot be always considered as models of(II) cannot be always considered as models ofAg(I) and Ag(I) and CdCd(II) cannot be always considered as models of (II) cannot be always considered as models of

Cu(I) and Zn(II) in MTs Cu(I) and Zn(II) in MTs In vivo In vivo formed species can be clearly different from those formed species can be clearly different from those

f df d i iti itformed formed in vitroin vitro The The stoichiometrystoichiometry of the species formed in a titration are not of the species formed in a titration are not

only dependent of the amount of metal presentonly dependent of the amount of metal presenty p py p p Zn(II) can play a structural role also in MTsZn(II) can play a structural role also in MTs The speed of metal replacement in MTs is dependent of The speed of metal replacement in MTs is dependent of

several factors (metal ion, protein, temperature, etc.)several factors (metal ion, protein, temperature, etc.) Evidence of the presence of SEvidence of the presence of S22-- ions as the third component ions as the third component

in metalin metal--MT complexes biosynthesized (recombinant andMT complexes biosynthesized (recombinant andin metalin metal MT complexes biosynthesized (recombinant and MT complexes biosynthesized (recombinant and native)native)

Metal specificity of each MT comes from their primary Metal specificity of each MT comes from their primary b t t f thb t t f th CC t t l ti iti it t l ti iti isequence but not from the sequence but not from the CysCys content or relative position in content or relative position in

the chainthe chain

Present and futurePresent and futurePresent and futurePresent and future Presence of S2- as additional ligands: Presence of S as additional ligands:◦ Structures of metal-S-MT species form◦ Role of S2-: redox process, homeostasis, etc.p , ,◦ Presence in other type of metallic complexes

Study of the interaction of MTs with other yproteins/species:◦ Interaction with radicals and role in the isomerization of

li idlipids◦ Reactivity with anticancer drugs (Pt, Ru, etc.)◦ Interaction with metalloproteins: hemocianin etc◦ Interaction with metalloproteins: hemocianin, etc.◦ Role in the detoxification of Pb(II) and Hg(II)Which is the role of MTs in each organism?

Which is their role in the different processesWhich is their role in the different processes where they can be found?

AcknowledgmentsAcknowledgmentsAcknowledgmentsAcknowledgmentsUNIVERSITAT DE BARCELONA

Ò. PalaciosR. OrihuelaM. TomasE. ArtellsS. Pérez-Rafael

C Pé ZúñiM. Capdevila

C. Pérez-Zúñiga

Projects: BIO2012-39682-C02-01 & 02

ColaboratorsColaboratorsColaboratorsColaborators

JHR Kägi W. Schaffner D. Winge V. PecoraroZürich,

SLC, Utah, Michigan

R. DallingerA TorreggianiJ M Domínguez

C. AndreoRosario,

Innsbruck,A. Torreggiani

Bologna,J. RuizMurcia

J.M. Domínguez-VeraGranada

MetallothioneinsMetallothioneins

The real stateThe real state--ofof--thethe--artartThe real stateThe real state--ofof--thethe--artart

Òscar PalaciosÒscar PalaciosDept QuímicaDept QuímicaDept. QuímicaDept. QuímicaUniversitat Autònoma de BarcelonaUniversitat Autònoma de Barcelona