Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins
Abstract
Zinc acquisition from limited environments is critical for bacterial survival and pathogenesis. AztD has been identified as a periplasmic or cell surface zinc-binding protein in numerous bacterial species. In Paracoccus denitrificans, AztD can transfer zinc directly to AztC, the solute binding protein for a zinc-specific ATP-binding cassette transporter system, suggesting a role in zinc acquisition and homeostasis. Here, we present the first cry stal structures of AztD from P. denitrificans and tbe human pathogen Citrobacter koseri, revealing a beta-propeller fold and two high-affinity zinc-binding sites that are highly conserved among AztD homologs. These structures combined with transfer assays using WT and mutant proteins provide rare insight into the mechanism of direct zinc transfer from one protein to another. Given the importance of zinc import to bacterial pathogenesis, these insights may prove valuable to the development of zinc transfer inhibitors as antibiotics.
- Authors:
-
[2];
[1]
- New Mexico State Univ., Las Cruces, NM (United States). Dept. of Chemistry and Biochemistry
- Reed College, Portland, OR (United States). Dept. of Chemistry
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); Howard Hughes Medical Institute
- OSTI Identifier:
- 1624533
- Grant/Contract Number:
- AC02-05CH11231; 1R01GM122819-01A
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Communications Biology
- Additional Journal Information:
- Journal Volume: 2; Journal Issue: 1; Journal ID: ISSN 2399-3642
- Publisher:
- Springer Nature
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Metals; X-ray Crystallography
Citation Formats
Neupane, Durga Prasad, Fullam, Stephanie Hope, Chacón, Kelly Natalia, and Yukl, Erik Thomas. Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins. United States: N. p., 2019.
Web. doi:10.1038/s42003-019-0542-z.
Neupane, Durga Prasad, Fullam, Stephanie Hope, Chacón, Kelly Natalia, & Yukl, Erik Thomas. Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins. United States. https://doi.org/10.1038/s42003-019-0542-z
Neupane, Durga Prasad, Fullam, Stephanie Hope, Chacón, Kelly Natalia, and Yukl, Erik Thomas. Fri .
"Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins". United States. https://doi.org/10.1038/s42003-019-0542-z. https://www.osti.gov/servlets/purl/1624533.
@article{osti_1624533,
title = {Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins},
author = {Neupane, Durga Prasad and Fullam, Stephanie Hope and Chacón, Kelly Natalia and Yukl, Erik Thomas},
abstractNote = {Zinc acquisition from limited environments is critical for bacterial survival and pathogenesis. AztD has been identified as a periplasmic or cell surface zinc-binding protein in numerous bacterial species. In Paracoccus denitrificans, AztD can transfer zinc directly to AztC, the solute binding protein for a zinc-specific ATP-binding cassette transporter system, suggesting a role in zinc acquisition and homeostasis. Here, we present the first cry stal structures of AztD from P. denitrificans and tbe human pathogen Citrobacter koseri, revealing a beta-propeller fold and two high-affinity zinc-binding sites that are highly conserved among AztD homologs. These structures combined with transfer assays using WT and mutant proteins provide rare insight into the mechanism of direct zinc transfer from one protein to another. Given the importance of zinc import to bacterial pathogenesis, these insights may prove valuable to the development of zinc transfer inhibitors as antibiotics.},
doi = {10.1038/s42003-019-0542-z},
journal = {Communications Biology},
number = 1,
volume = 2,
place = {United States},
year = {2019},
month = {8}
}
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Works referenced in this record:
Two ABC Transporters and a Periplasmic Metallochaperone Participate in Zinc Acquisition in Paracoccus denitrificans
journal, October 2018
- Neupane, Durga P.; Kumar, Santosh; Yukl, Erik T.
- Biochemistry, Vol. 58, Issue 2
His-tags as Zn(II) binding motifs in a protein-based fluorescent sensor
journal, May 2008
- Evers, T. H.; Appelhof, M. A. M.; Meijer, E. W.
- Protein Engineering Design and Selection, Vol. 21, Issue 8
Mechanisms of zinc binding to the solute-binding protein AztC and transfer from the metallochaperone AztD
journal, September 2017
- Neupane, Durga P.; Avalos, Dante; Fullam, Stephanie
- Journal of Biological Chemistry, Vol. 292, Issue 42
Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks
journal, August 2015
- Gerlt, John A.; Bouvier, Jason T.; Davidson, Daniel B.
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1854, Issue 8
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
The anatomy of a bifunctional enzyme: Structural basis for reduction of oxygen to water and synthesis of nitric oxide by cytochrome cd1
journal, May 1995
- Fülöp, Vilmos; Moir, James W. B.; Ferguson, Stuart J.
- Cell, Vol. 81, Issue 3
Metal Binding Studies and EPR Spectroscopy of the Manganese Transport Regulator MntR †
journal, December 2006
- Golynskiy, Misha V.; Gunderson, William A.; Hendrich, Michael P.
- Biochemistry, Vol. 45, Issue 51
Dali server update
journal, April 2016
- Holm, Liisa; Laakso, Laura M.
- Nucleic Acids Research, Vol. 44, Issue W1
Identification of an Acinetobacter baumannii Zinc Acquisition System that Facilitates Resistance to Calprotectin-mediated Zinc Sequestration
journal, December 2012
- Hood, M. Indriati; Mortensen, Brittany L.; Moore, Jessica L.
- PLoS Pathogens, Vol. 8, Issue 12
Dali server: conservation mapping in 3D
journal, May 2010
- Holm, Liisa; Rosenstr�m, P�ivi
- Nucleic Acids Research, Vol. 38, Issue suppl_2
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard
journal, December 2007
- Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.
- Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1
ABC transporter architecture and regulatory roles of accessory domains
journal, December 2005
- Biemans-Oldehinkel, Esther; Doeven, Mark K.; Poolman, Bert
- FEBS Letters, Vol. 580, Issue 4
Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc
journal, February 2018
- Cao, Kun; Li, Nan; Wang, Hongcui
- Journal of Biological Chemistry, Vol. 293, Issue 16
Crystal structure of an electron-transfer complex between methylamine dehydrogenase and amicyanin
journal, June 1992
- Chen, Longyin; Durley, Rosemary; Poliks, Barbara J.
- Biochemistry, Vol. 31, Issue 21
Bacterial zinc uptake regulator proteins and their regulons
journal, July 2018
- Mikhaylina, Alevtina; Ksibe, Amira Z.; Scanlan, David J.
- Biochemical Society Transactions, Vol. 46, Issue 4
Structure of a quinohemoprotein amine dehydrogenase with an uncommon redox cofactor and highly unusual crosslinking
journal, November 2001
- Datta, S.; Mori, Y.; Takagi, K.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 25
An Antimicrobial Role for Zinc in Innate Immune Defense Against Group A Streptococcus
journal, January 2014
- Ong, Cheryl-lynn Y.; Gillen, Christine M.; Barnett, Timothy C.
- The Journal of Infectious Diseases, Vol. 209, Issue 10
A structural classification of substrate-binding proteins
journal, April 2010
- Berntsson, Ronnie P. -A.; Smits, Sander H. J.; Schmitt, Lutz
- FEBS Letters, Vol. 584, Issue 12
Structural mechanisms of heavy-metal extrusion by the Cus efflux system
journal, May 2013
- Delmar, Jared A.; Su, Chih-Chia; Yu, Edward W.
- BioMetals, Vol. 26, Issue 4
Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard
journal, May 2009
- Terwilliger, Thomas C.; Adams, Paul D.; Read, Randy J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 6
ABC Transporters: From Microorganisms to Man
journal, November 1992
- Higgins, C. F.
- Annual Review of Cell Biology, Vol. 8, Issue 1
AztD, a Periplasmic Zinc Metallochaperone to an ATP-binding Cassette (ABC) Transporter System in Paracoccus denitrificans
journal, October 2015
- Handali, Melody; Roychowdhury, Hridindu; Neupane, Durga P.
- Journal of Biological Chemistry, Vol. 290, Issue 50
Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling
journal, April 2006
- Masgrau, L.
- Science, Vol. 312, Issue 5771
Transcriptional Regulation, Metal Binding Properties and Structure of Pden1597, an Unusual Zinc Transport Protein from Paracoccus denitrificans
journal, March 2015
- Handali, Melody; Neupane, Durga P.; Roychowdhury, Hridindu
- Journal of Biological Chemistry, Vol. 290, Issue 19
Nutritional immunity beyond iron: a role for manganese and zinc
journal, April 2010
- Kehl-Fie, Thomas E.; Skaar, Eric P.
- Current Opinion in Chemical Biology, Vol. 14, Issue 2
Models for the Metal Transfer Complex of the N-Terminal Region of CusB and CusF
journal, June 2015
- Ucisik, Melek N.; Chakravorty, Dhruva K.; Merz, Kenneth M.
- Biochemistry, Vol. 54, Issue 27
The Salmonella enterica ZinT structure, zinc affinity and interaction with the high-affinity uptake protein ZnuA provide insight into the management of periplasmic zinc
journal, January 2014
- Ilari, Andrea; Alaleona, Flaminia; Tria, Giancarlo
- Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1840, Issue 1
Integration, scaling, space-group assignment and post-refinement
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
The Zur-Regulated ZinT Protein Is an Auxiliary Component of the High-Affinity ZnuABC Zinc Transporter That Facilitates Metal Recruitment during Severe Zinc Shortage
journal, January 2010
- Petrarca, P.; Ammendola, S.; Pasquali, P.
- Journal of Bacteriology, Vol. 192, Issue 6
New Insights into Histidine Triad Proteins: Solution Structure of a Streptococcus pneumoniae PhtD Domain and Zinc Transfer to AdcAII
journal, November 2013
- Bersch, Beate; Bougault, Catherine; Roux, Laure
- PLoS ONE, Vol. 8, Issue 11
The Pfam protein families database in 2019
journal, October 2018
- El-Gebali, Sara; Mistry, Jaina; Bateman, Alex
- Nucleic Acids Research, Vol. 47, Issue D1
Tracking metal ions through a Cu/Ag efflux pump assigns the functional roles of the periplasmic proteins
journal, October 2014
- Chacon, K. N.; Mealman, T. D.; McEvoy, M. M.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 43
Chaperone-mediated copper handling in the periplasm
journal, January 2010
- Kim, Eun-Hae; Rensing, Christopher; McEvoy, Megan M.
- Natural Product Reports, Vol. 27, Issue 5
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
WD40 Repeat Proteins: Signalling Scaffold with Diverse Functions
journal, August 2018
- Jain, Buddhi Prakash; Pandey, Shweta
- The Protein Journal, Vol. 37, Issue 5
Bacterial Strategies to Maintain Zinc Metallostasis at the Host-Pathogen Interface
journal, July 2016
- Capdevila, Daiana A.; Wang, Jiefei; Giedroc, David P.
- Journal of Biological Chemistry, Vol. 291, Issue 40
Zinc and copper toxicity in host defense against pathogens: Mycobacterium tuberculosis as a model example of an emerging paradigm
journal, January 2013
- Neyrolles, Olivier; Mintz, Elisabeth; Catty, Patrice
- Frontiers in Cellular and Infection Microbiology, Vol. 3
Comparative genomics of bacterial zinc regulons: Enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins
journal, August 2003
- Panina, E. M.; Mironov, A. A.; Gelfand, M. S.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 17
A subset of the diverse COG0523 family of putative metal chaperones is linked to zinc homeostasis in all kingdoms of life
journal, January 2009
- Haas, Crysten E.; Rodionov, Dmitry A.; Kropat, Janette
- BMC Genomics, Vol. 10, Issue 1
Direct Metal Transfer between Periplasmic Proteins Identifies a Bacterial Copper Chaperone †
journal, November 2008
- Bagai, Ireena; Rensing, Christopher; Blackburn, Ninian J.
- Biochemistry, Vol. 47, Issue 44
Spectroscopic Determination of Tryptophan and Tyrosine in Proteins *
journal, July 1967
- Edelhoch, Harold
- Biochemistry, Vol. 6, Issue 7
Zinc Coordination Spheres in Protein Structures
journal, October 2013
- Laitaoja, Mikko; Valjakka, Jarkko; Jänis, Janne
- Inorganic Chemistry, Vol. 52, Issue 19
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks
journal, November 2003
- Shannon, P.
- Genome Research, Vol. 13, Issue 11
Role of ZnuABC and ZinT in Escherichia coli O157:H7 zinc acquisition and interaction with epithelial cells
journal, January 2011
- Gabbianelli, Roberta; Scotti, Raffaella; Ammendola, Serena
- BMC Microbiology, Vol. 11, Issue 1
‘Democratized’ genomic enzymology web tools for functional assignment
journal, December 2018
- Zallot, Rémi; Oberg, Nils O.; Gerlt, John A.
- Current Opinion in Chemical Biology, Vol. 47
The First Histidine Triad Motif of PhtD Is Critical for Zinc Homeostasis in Streptococcus pneumoniae
journal, November 2015
- Eijkelkamp, Bart A.; Pederick, Victoria G.; Plumptre, Charles D.
- Infection and Immunity, Vol. 84, Issue 2
Metal Binding Properties of Escherichia coli YjiA, a Member of the Metal Homeostasis-Associated COG0523 Family of GTPases
journal, February 2013
- Sydor, Andrew M.; Jost, Marco; Ryan, Katherine S.
- Biochemistry, Vol. 52, Issue 10
Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega
journal, January 2011
- Sievers, Fabian; Wilm, Andreas; Dineen, David
- Molecular Systems Biology, Vol. 7, Issue 1
Trapping intermediates in metal transfer reactions of the CusCBAF export pump of Escherichia coli
journal, November 2018
- Chacón, Kelly N.; Perkins, Jonathan; Mathe, Zachary
- Communications Biology, Vol. 1, Issue 1
A new family of high-affinity ABC manganese and zinc permeases
journal, April 2001
- Claverys, Jean-Pierre
- Research in Microbiology, Vol. 152, Issue 3-4
The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes
journal, February 2016
- van Zundert, G. C. P.; Rodrigues, J. P. G. L. M.; Trellet, M.
- Journal of Molecular Biology, Vol. 428, Issue 4
Pneumococcal histidine triad proteins are regulated by the Zn 2+ ‐dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H
journal, October 2008
- Ogunniyi, Abiodun D.; Grabowicz, Marcin; Mahdi, Layla K.
- The FASEB Journal, Vol. 23, Issue 3
The Cus efflux system removes toxic ions via a methionine shuttle: The Cus Efflux System
journal, November 2010
- Su, Chih-Chia; Long, Feng; Yu, Edward W.
- Protein Science, Vol. 20, Issue 1
AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in S treptococcus pneumoniae: AdcA and pneumococcal zinc homeostasis
journal, January 2014
- Plumptre, Charles D.; Eijkelkamp, Bart A.; Morey, Jacqueline R.
- Molecular Microbiology, Vol. 91, Issue 4
Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence–Function Space and Genome Context to Discover Novel Functions
journal, August 2017
- Gerlt, John A.
- Biochemistry, Vol. 56, Issue 33
Bacterial ATP-driven transporters of transition metals: physiological roles, mechanisms of action, and roles in bacterial virulence
journal, January 2011
- Klein, Joshua S.; Lewinson, Oded
- Metallomics, Vol. 3, Issue 11
The X-ray Structure of the Zinc Transporter ZnuA from Salmonella enterica Discloses a Unique Triad of Zinc-Coordinating Histidines
journal, June 2011
- Ilari, Andrea; Alaleona, Flaminia; Petrarca, Patrizia
- Journal of Molecular Biology, Vol. 409, Issue 4
Zinc-Dependent Transcriptional Regulation in Paracoccus denitrificans
journal, April 2017
- Neupane, Durga P.; Jacquez, Belkis; Sundararajan, Anitha
- Frontiers in Microbiology, Vol. 8
Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses
journal, February 2008
- Corbin, Brian D.; Seeley, Erin H.; Raab, Andrea
- Science, Vol. 319, Issue 5865
Program DYNAFIT for the Analysis of Enzyme Kinetic Data: Application to HIV Proteinase
journal, June 1996
- Kuzmič, Petr
- Analytical Biochemistry, Vol. 237, Issue 2
MOLEonline: a web-based tool for analyzing channels, tunnels and pores (2018 update)
journal, April 2018
- Pravda, Lukáš; Sehnal, David; Toušek, Dominik
- Nucleic Acids Research, Vol. 46, Issue W1
Severe Zinc Depletion of Escherichia coli: ROLES FOR HIGH AFFINITY ZINC BINDING BY ZinT, ZINC TRANSPORT AND ZINC-INDEPENDENT PROTEINS
journal, April 2009
- Graham, Alison I.; Hunt, Stuart; Stokes, Sarah L.
- Journal of Biological Chemistry, Vol. 284, Issue 27
Jalview Version 2--a multiple sequence alignment editor and analysis workbench
journal, January 2009
- Waterhouse, A. M.; Procter, J. B.; Martin, D. M. A.
- Bioinformatics, Vol. 25, Issue 9
A deliberate approach to screening for initial crystallization conditions of biological macromolecules
journal, April 2003
- Luft, Joseph R.; Collins, Robert J.; Fehrman, Nancy A.
- Journal of Structural Biology, Vol. 142, Issue 1
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
HADDOCK: A Protein−Protein Docking Approach Based on Biochemical or Biophysical Information
journal, February 2003
- Dominguez, Cyril; Boelens, Rolf; Bonvin, Alexandre M. J. J.
- Journal of the American Chemical Society, Vol. 125, Issue 7
Structure and mechanism of the tripartite CusCBA heavy-metal efflux complex
journal, April 2012
- Long, Feng; Su, Chih-Chia; Lei, Hsiang-Ting
- Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 367, Issue 1592
Why does the Aβ peptide of Alzheimer share structural similarity with antimicrobial peptides?
journal, March 2020
- Pastore, Annalisa; Raimondi, Francesco; Rajendran, Lawrence
- Communications Biology, Vol. 3, Issue 1
A Novel Type of Catalytic Copper Cluster in Nitrous Oxide Reductase
journal, August 2000
- Brown, K.; Tegoni, M.; Prudêncio, M.
- Acta Crystallographica Section A Foundations of Crystallography, Vol. 56, Issue s1
Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard.
text, January 2009
- Terwilliger, Thomas C.; Adams, Paul D.; Read, Randy
- Apollo - University of Cambridge Repository
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