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Title: A new metal binding domain involved in cadmium, cobalt and zinc transport

Abstract

The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, but bioinformatics analyses indicate that a diversity of MBDs may exist in nature. In this paper, we report the biochemical, structural and functional characterization of a new MBD from the Cupriavidus metallidurans P1B-4-ATPase CzcP (CzcP MBD). The CzcP MBD binds two Cd2+, Co2+ or Zn2+ ions in distinct and unique sites and adopts an unexpected fold consisting of two fused ferredoxin-like domains. Both in vitro and in vivo activity assays using full-length CzcP, truncated CzcP and several variants indicate a regulatory role for the MBD and distinct functions for the two metal binding sites. Finally, taken together, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P1B-ATPases.

Authors:
 [1];  [2];  [2];  [1]
  1. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences. Dept. of Chemistry
  2. Wayne State Univ., Detroit, MI (United States). School of Medicine. Dept. of Pharmaceutical Sciences. Cardiovascular Research Inst.
Publication Date:
Research Org.:
Northwestern Univ., Evanston, IL (United States)
Sponsoring Org.:
USDOE; National Inst. of Health (NIH) (United States)
Contributing Org.:
Wayne State Univ., Detroit, MI (United States)
OSTI Identifier:
1213727
Grant/Contract Number:  
AC02-98CH10886; GM58518; DK068139; F32GM105339; T32HL120822
Resource Type:
Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 11; Journal Issue: 9; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Bioinorganic chemistry; Metals; Transporters; X-ray crystallography

Citation Formats

Smith, Aaron T., Barupala, Dulmini, Stemmler, Timothy L., and Rosenzweig, Amy C. A new metal binding domain involved in cadmium, cobalt and zinc transport. United States: N. p., 2015. Web. doi:10.1038/nchembio.1863.
Smith, Aaron T., Barupala, Dulmini, Stemmler, Timothy L., & Rosenzweig, Amy C. A new metal binding domain involved in cadmium, cobalt and zinc transport. United States. https://doi.org/10.1038/nchembio.1863
Smith, Aaron T., Barupala, Dulmini, Stemmler, Timothy L., and Rosenzweig, Amy C. Mon . "A new metal binding domain involved in cadmium, cobalt and zinc transport". United States. https://doi.org/10.1038/nchembio.1863. https://www.osti.gov/servlets/purl/1213727.
@article{osti_1213727,
title = {A new metal binding domain involved in cadmium, cobalt and zinc transport},
author = {Smith, Aaron T. and Barupala, Dulmini and Stemmler, Timothy L. and Rosenzweig, Amy C.},
abstractNote = {The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, but bioinformatics analyses indicate that a diversity of MBDs may exist in nature. In this paper, we report the biochemical, structural and functional characterization of a new MBD from the Cupriavidus metallidurans P1B-4-ATPase CzcP (CzcP MBD). The CzcP MBD binds two Cd2+, Co2+ or Zn2+ ions in distinct and unique sites and adopts an unexpected fold consisting of two fused ferredoxin-like domains. Both in vitro and in vivo activity assays using full-length CzcP, truncated CzcP and several variants indicate a regulatory role for the MBD and distinct functions for the two metal binding sites. Finally, taken together, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P1B-ATPases.},
doi = {10.1038/nchembio.1863},
journal = {Nature Chemical Biology},
number = 9,
volume = 11,
place = {United States},
year = {Mon Jul 20 00:00:00 EDT 2015},
month = {Mon Jul 20 00:00:00 EDT 2015}
}

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Works referenced in this record:

Structure and Ubiquitin Interactions of the Conserved Zinc Finger Domain of Npl4
journal, March 2003

  • Wang, Bin; Alam, Steven L.; Meyer, Hemmo H.
  • Journal of Biological Chemistry, Vol. 278, Issue 22
  • DOI: 10.1074/jbc.M300459200

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn 2+ -ATPase HMA2
journal, September 2006

  • Eren, Elif; Kennedy, David C.; Maroney, Michael J.
  • Journal of Biological Chemistry, Vol. 281, Issue 45
  • DOI: 10.1074/jbc.M605218200

Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

The structure and function of heavy metal transport P1B-ATPases
journal, January 2007


Structural Basis for Metal Binding Specificity: the N-terminal Cadmium Binding Domain of the P1-type ATPase CadA
journal, February 2006

  • Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone
  • Journal of Molecular Biology, Vol. 356, Issue 3
  • DOI: 10.1016/j.jmb.2005.11.055

PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787

Differential roles for the Co 2+ /Ni 2+ transporting ATPases, CtpD and CtpJ, in Mycobacterium tuberculosis virulence: CtpD is uniquely required for infection
journal, November 2013

  • Raimunda, Daniel; Long, Jarukit E.; Padilla-Benavides, Teresita
  • Molecular Microbiology, Vol. 91, Issue 1
  • DOI: 10.1111/mmi.12454

Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake
journal, March 2006

  • Achila, D.; Banci, L.; Bertini, I.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 15
  • DOI: 10.1073/pnas.0504472103

Bacterial Transition Metal P 1B -ATPases: Transport Mechanism and Roles in Virulence
journal, November 2011

  • Argüello, José M.; González-Guerrero, Manuel; Raimunda, Daniel
  • Biochemistry, Vol. 50, Issue 46
  • DOI: 10.1021/bi201418k

Characterization of a Cobalt-Specific P 1B -ATPase
journal, September 2012

  • Zielazinski, Eliza L.; Cutsail, George E.; Hoffman, Brian M.
  • Biochemistry, Vol. 51, Issue 40
  • DOI: 10.1021/bi3006708

Characterization of a Thermophilic P-type Ag + /Cu + -ATPase from the Extremophile Archaeoglobus fulgidus
journal, December 2001

  • Mandal, Atin K.; Cheung, Win D.; Argüello, José M.
  • Journal of Biological Chemistry, Vol. 277, Issue 9
  • DOI: 10.1074/jbc.M109964200

Atx1-like chaperones and their cognate P-type ATPases: copper-binding and transfer
journal, January 2007


Structure and mechanism of Zn2+-transporting P-type ATPases
journal, August 2014

  • Wang, Kaituo; Sitsel, Oleg; Meloni, Gabriele
  • Nature, Vol. 514, Issue 7523
  • DOI: 10.1038/nature13618

A new structural paradigm in copper resistance in Streptococcus pneumoniae
journal, January 2013

  • Fu, Yue; Tsui, Ho-Ching Tiffany; Bruce, Kevin E.
  • Nature Chemical Biology, Vol. 9, Issue 3
  • DOI: 10.1038/nchembio.1168

P1B-ATPases – an ancient family of transition metal pumps with diverse functions in plants
journal, October 2005


On Allosteric Modulation of P-Type Cu+-ATPases
journal, July 2013

  • Mattle, Daniel; Sitsel, Oleg; Autzen, Henriette E.
  • Journal of Molecular Biology, Vol. 425, Issue 13
  • DOI: 10.1016/j.jmb.2013.03.008

P-Type ATPases
journal, June 2011


Crystal structure of a copper-transporting PIB-type ATPase
journal, June 2011

  • Gourdon, Pontus; Liu, Xiang-Yu; Skjørringe, Tina
  • Nature, Vol. 475, Issue 7354
  • DOI: 10.1038/nature10191

Solution Structure of the Yeast Copper Transporter Domain Ccc2a in the Apo and Cu(I)-loaded States
journal, November 2000

  • Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone
  • Journal of Biological Chemistry, Vol. 276, Issue 11
  • DOI: 10.1074/jbc.M008389200

JLigand : a graphical tool for the CCP 4 template-restraint library
journal, March 2012

  • Lebedev, Andrey A.; Young, Paul; Isupov, Michail N.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
  • DOI: 10.1107/S090744491200251X

Copper-transporting P-type ATPases use a unique ion-release pathway
journal, December 2013

  • Andersson, Magnus; Mattle, Daniel; Sitsel, Oleg
  • Nature Structural & Molecular Biology, Vol. 21, Issue 1
  • DOI: 10.1038/nsmb.2721

CzcE from Cupriavidus metallidurans CH34 is a copper-binding protein
journal, January 2008

  • Zoropogui, Anthony; Gambarelli, Serge; Covès, Jacques
  • Biochemical and Biophysical Research Communications, Vol. 365, Issue 4
  • DOI: 10.1016/j.bbrc.2007.11.030

Protein secondary structure analyses from circular dichroism spectroscopy: Methods and reference databases
journal, May 2008

  • Whitmore, Lee; Wallace, B. A.
  • Biopolymers, Vol. 89, Issue 5, p. 392-400
  • DOI: 10.1002/bip.20853

xia2 : an expert system for macromolecular crystallography data reduction
journal, December 2009


Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

A Combined Zinc/Cadmium Sensor and Zinc/Cadmium Export Regulator in a Heavy Metal Pump
journal, July 2010

  • Bækgaard, Lone; Mikkelsen, Maria D.; Sørensen, Danny M.
  • Journal of Biological Chemistry, Vol. 285, Issue 41
  • DOI: 10.1074/jbc.M110.111260

Evolution of Copper Transporting ATPases in Eukaryotic Organisms
journal, April 2012


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Identification of a Hemerythrin-like Domain in a P 1B -Type Transport ATPase
journal, August 2010

  • Traverso, Matthew E.; Subramanian, Poorna; Davydov, Roman
  • Biochemistry, Vol. 49, Issue 33
  • DOI: 10.1021/bi100866b

CzcP is a novel efflux system contributing to transition metal resistance in Cupriavidus metallidurans CH34
journal, August 2009


Structural Biology of Copper Trafficking
journal, October 2009

  • Boal, Amie K.; Rosenzweig, Amy C.
  • Chemical Reviews, Vol. 109, Issue 10
  • DOI: 10.1021/cr900104z

Identification of Ion-Selectivity Determinants in Heavy-Metal Transport P 1B -type ATPases
journal, September 2003


Evidence for Conformational Changes upon Copper Binding to Cupriavidus metallidurans CzcE
journal, March 2010

  • Petit-Haertlein, Isabelle; Girard, Eric; Sarret, Géraldine
  • Biochemistry, Vol. 49, Issue 9
  • DOI: 10.1021/bi100001z

Diversity of the metal-transporting P1B-type ATPases
journal, April 2014

  • Smith, Aaron T.; Smith, Kyle P.; Rosenzweig, Amy C.
  • JBIC Journal of Biological Inorganic Chemistry, Vol. 19, Issue 6
  • DOI: 10.1007/s00775-014-1129-2

Metal-dependent folding of a single zinc finger from transcription factor IIIA.
journal, July 1987

  • Frankel, A. D.; Berg, J. M.; Pabo, C. O.
  • Proceedings of the National Academy of Sciences, Vol. 84, Issue 14
  • DOI: 10.1073/pnas.84.14.4841

A new structural paradigm in copper resistance in Streptococcus pneumoniae
journal, January 2013

  • Fu, Yue; Tsui, Ho-Ching Tiffany; Bruce, Kevin E.
  • Nature Chemical Biology, Vol. 9, Issue 3
  • DOI: 10.1038/nchembio.1168

Atx1-like chaperones and their cognate P-type ATPases: copper-binding and transfer
journal, January 2007


Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease
journal, October 2005

  • DeSilva, Tara M.; Veglia, Gianluigi; Opella, Stanley J.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 61, Issue 4
  • DOI: 10.1002/prot.20639

An improved assay for nanomole amounts of inorganic phosphate
journal, November 1979


Role in metal homeostasis of CtpD, a Co2+ transporting P1B4-ATPase of Mycobacterium smegmatis: Mycobacteria Co2+-ATPase
journal, May 2012


Characterization of a Cobalt-Specific P 1B -ATPase
journal, September 2012

  • Zielazinski, Eliza L.; Cutsail, George E.; Hoffman, Brian M.
  • Biochemistry, Vol. 51, Issue 40
  • DOI: 10.1021/bi3006708

The ATP Hydrolytic Activity of Purified ZntA, a Pb(II)/Cd(II)/Zn(II)-translocating ATPase from Escherichia coli
journal, February 2000

  • Sharma, Rakesh; Rensing, Christopher; Rosen, Barry P.
  • Journal of Biological Chemistry, Vol. 275, Issue 6
  • DOI: 10.1074/jbc.275.6.3873

The structure and function of heavy metal transport P1B-ATPases
journal, January 2007


Structural Basis for Metal Binding Specificity: the N-terminal Cadmium Binding Domain of the P1-type ATPase CadA
journal, February 2006

  • Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone
  • Journal of Molecular Biology, Vol. 356, Issue 3
  • DOI: 10.1016/j.jmb.2005.11.055

Copper-transporting P-type ATPases use a unique ion-release pathway
journal, December 2013

  • Andersson, Magnus; Mattle, Daniel; Sitsel, Oleg
  • Nature Structural & Molecular Biology, Vol. 21, Issue 1
  • DOI: 10.1038/nsmb.2721

Bacterial Transition Metal P 1B -ATPases: Transport Mechanism and Roles in Virulence
journal, November 2011

  • Argüello, José M.; González-Guerrero, Manuel; Raimunda, Daniel
  • Biochemistry, Vol. 50, Issue 46
  • DOI: 10.1021/bi201418k

Plasmids pMOL28 and pMOL30 of Cupriavidus metallidurans Are Specialized in the Maximal Viable Response to Heavy Metals
journal, August 2007

  • Monchy, S.; Benotmane, M. A.; Janssen, P.
  • Journal of Bacteriology, Vol. 189, Issue 20
  • DOI: 10.1128/jb.00375-07

Metal-dependent folding of a single zinc finger from transcription factor IIIA.
journal, July 1987

  • Frankel, A. D.; Berg, J. M.; Pabo, C. O.
  • Proceedings of the National Academy of Sciences, Vol. 84, Issue 14
  • DOI: 10.1073/pnas.84.14.4841

On Allosteric Modulation of P-Type Cu+-ATPases
journal, July 2013

  • Mattle, Daniel; Sitsel, Oleg; Autzen, Henriette E.
  • Journal of Molecular Biology, Vol. 425, Issue 13
  • DOI: 10.1016/j.jmb.2013.03.008

Extended x-ray absorption fine structure—its strengths and limitations as a structural tool
journal, October 1981


Structure and mechanism of Zn2+-transporting P-type ATPases
journal, August 2014

  • Wang, Kaituo; Sitsel, Oleg; Meloni, Gabriele
  • Nature, Vol. 514, Issue 7523
  • DOI: 10.1038/nature13618

Identification of Ion-Selectivity Determinants in Heavy-Metal Transport P 1B -type ATPases
journal, September 2003


Functional Roles of Metal Binding Domains of the Archaeoglobus fulgidus Cu + -ATPase CopA
journal, September 2003

  • Mandal, Atin K.; Argüello, José M.
  • Biochemistry, Vol. 42, Issue 37
  • DOI: 10.1021/bi034806y

A New Zinc–protein Coordination Site in Intracellular Metal Trafficking: Solution Structure of the Apo and Zn(II) forms of ZntA(46–118)
journal, November 2002


P-Type ATPases
book, January 2016


P-type ATPases
journal, December 1996


DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data
journal, July 2004

  • Whitmore, L.; Wallace, B. A.
  • Nucleic Acids Research, Vol. 32, Issue S2, p. W668-W673
  • DOI: 10.1093/nar/gkh371

Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021


Zinc metalloproteins involved in replication and transcription
journal, October 1986

  • Giedroc, David P.; Keating, Kathleen M.; Martin, Craig T.
  • Journal of Inorganic Biochemistry, Vol. 28, Issue 2-3
  • DOI: 10.1016/0162-0134(86)80079-4

P-Type ATPases
journal, June 2011


REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011

  • Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444911001314

An improved assay for nanomole amounts of inorganic phosphate
journal, November 1979


P1B-ATPases – an ancient family of transition metal pumps with diverse functions in plants
journal, October 2005


Cellular multitasking: The dual role of human Cu-ATPases in cofactor delivery and intracellular copper balance
journal, August 2008

  • Lutsenko, Svetlana; Gupta, Arnab; Burkhead, Jason L.
  • Archives of Biochemistry and Biophysics, Vol. 476, Issue 1
  • DOI: 10.1016/j.abb.2008.05.005

Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease
journal, October 2005

  • DeSilva, Tara M.; Veglia, Gianluigi; Opella, Stanley J.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 61, Issue 4
  • DOI: 10.1002/prot.20639

Overview of the CCP4 suite and current developments.
text, January 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.52322

CzcE from Cupriavidus metallidurans CH34 is a copper-binding protein
journal, January 2008

  • Zoropogui, Anthony; Gambarelli, Serge; Covès, Jacques
  • Biochemical and Biophysical Research Communications, Vol. 365, Issue 4
  • DOI: 10.1016/j.bbrc.2007.11.030

Structural Biology of Copper Trafficking
journal, October 2009

  • Boal, Amie K.; Rosenzweig, Amy C.
  • Chemical Reviews, Vol. 109, Issue 10
  • DOI: 10.1021/cr900104z

Functional Roles of Metal Binding Domains of the Archaeoglobus fulgidus Cu + -ATPase CopA
journal, September 2003

  • Mandal, Atin K.; Argüello, José M.
  • Biochemistry, Vol. 42, Issue 37
  • DOI: 10.1021/bi034806y

Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake
journal, March 2006

  • Achila, D.; Banci, L.; Bertini, I.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 15
  • DOI: 10.1073/pnas.0504472103

Relativistic calculations of spin-dependent x-ray-absorption spectra
journal, July 1997


Archaeoglobus fulgidus CopB Is a Thermophilic Cu 2+ -ATPase : FUNCTIONAL ROLE OF ITS HISTIDINE-RICH N-TERMINAL METAL BINDING DOMAIN
journal, July 2003

  • Mana-Capelli, Sebastián; Mandal, Atin K.; Argüello, José M.
  • Journal of Biological Chemistry, Vol. 278, Issue 42
  • DOI: 10.1074/jbc.M306907200

Spectroscopic properties of the alpha fragment of metallothionein.
journal, November 1984


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Novel and efficient screening of PQQ high-yielding strains and subsequent cultivation optimization
journal, July 2016

  • Si, Zhenjun; Zhu, Jianzhong; Wang, Wenguang
  • Applied Microbiology and Biotechnology, Vol. 100, Issue 24
  • DOI: 10.1007/s00253-016-7739-6

Unique roles of iron and zinc binding to the yeast Fe–S cluster scaffold assembly protein “Isu1”
journal, January 2019

  • Lewis, Brianne E.; Mason, Zachary; Rodrigues, Andria V.
  • Metallomics, Vol. 11, Issue 11
  • DOI: 10.1039/c9mt00172g

Characterization of a promiscuous cadmium and arsenic resistance mechanism in Thermus thermophilus HB27 and potential application of a novel bioreporter system
journal, May 2018

  • Antonucci, Immacolata; Gallo, Giovanni; Limauro, Danila
  • Microbial Cell Factories, Vol. 17, Issue 1
  • DOI: 10.1186/s12934-018-0918-7

Characterization of a promiscuous cadmium and arsenic resistance mechanism in Thermus thermophilus HB27 and potential application of a novel bioreporter system
journal, May 2018

  • Antonucci, Immacolata; Gallo, Giovanni; Limauro, Danila
  • Microbial Cell Factories, Vol. 17, Issue 1
  • DOI: 10.1186/s12934-018-0918-7

Characterization of the heavy metal binding properties of periplasmic metal uptake protein CLas-ZnuA2
journal, January 2020

  • Kumar, Pranav; Dalal, Vikram; Sharma, Nidhi
  • Metallomics, Vol. 12, Issue 2
  • DOI: 10.1039/c9mt00200f

Cu + -specific CopB transporter: Revising P 1B -type ATPase classification
journal, February 2018

  • Purohit, Rahul; Ross, Matthew O.; Batelu, Sharon
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 9
  • DOI: 10.1073/pnas.1721783115