The S2 Cu(i) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance

Metallomics : Integrated Biometal Science
Yue FuDavid P Giedroc

Abstract

Pathogenic bacteria have evolved copper homeostasis and resistance systems for fighting copper toxicity imposed by the human immune system. Streptococcus pneumoniae is a respiratory pathogen that encodes an obligatorily membrane-anchored Cu(i) binding protein, CupA, and a P1B-type ATPase efflux transporter, CopA. The soluble, cytoplasmic domain of CupA (sCupA) contains a binuclear Cu(i) cluster consisting of S1 and S2 Cu(i) ions. The NMR solution structure of apo-sCupA reveals the same cupredoxin fold of Cu2-sCupA, except that the Cu(i) binding loop (residues 112-116, harboring S2 Cu ligands M113 and M115) is highly dynamic as documented by both backbone and side chain methionine methyl order parameters. In contrast to the more solvent exposed, lower affinity S2 Cu site, the high affinity S1 Cu-coordinating cysteines (C74, C111) are pre-organized in the apo-sCupA structure. Biological experiments reveal that the S1 site is largely dispensable for cellular Cu resistance and may be involved in buffering low cytoplasmic Cu(i). In contrast, the S2 site is essential for Cu resistance. Expression of a chimeric CopZ chaperone fused to the CupA transmembrane helix does not protect S. pneumoniae from copper toxicity and substitution of ...Continue Reading

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Nov 21, 1997·Journal of Molecular Biology·P GüntertK Wüthrich
Jun 9, 1999·Nature Structural Biology·P A WilliamsD E McRee
Apr 1, 2000·Current Opinion in Chemical Biology·A C Rosenzweig, T V O'Halloran
Dec 19, 2001·Biochemistry·L BanciF J Ruiz-Dueñas
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
May 15, 2003·The Journal of Biological Chemistry·Zhanjun Hou, Bharati Mitra
Jun 1, 2006·Journal of the American Chemical Society·Vitali Tugarinov, Lewis E Kay
Dec 23, 2006·Proteins·Aneerban BhattacharyaGaetano T Montelione
Jan 26, 2007·Journal of the American Chemical Society·Vitali TugarinovLewis E Kay
Apr 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Manuel González-Guerrero, José M Argüello
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lee Macomber, James A Imlay
Oct 8, 2009·The Journal of Biological Chemistry·Carine WhiteMichael J Petris
Oct 15, 2009·Chemical Reviews·Amie K Boal, Amy C Rosenzweig
Mar 9, 2010·Annual Review of Biochemistry·Nigel J Robinson, Dennis R Winge
Apr 13, 2010·Nature Chemical Biology·Michael S MarlowA Joshua Wand
Feb 1, 2011·Metallomics : Integrated Biometal Science·Faith E JacobsenDavid P Giedroc
Mar 3, 2011·Biochemical and Biophysical Research Communications·Mauricio LatorreMauricio González
Apr 23, 2011·Biophysical Chemistry·Hermes Reyes-CaballeroDavid P Giedroc
Jul 1, 2011·Nature·Pontus GourdonPoul Nissen
Dec 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Steve TotteyNigel J Robinson
Nov 28, 2012·The Journal of Biological Chemistry·Teresita Padilla-BenavidesJosé M Argüello
Jan 29, 2013·Nature Chemical Biology·Yue FuDavid P Giedroc
Jun 7, 2013·Bioscience Reports·Sian L StaffordMatthew J Sweet
Jul 31, 2013·ACS Chemical Biology·Karrera Y Djoko, Alastair G McEwan
Jan 28, 2014·Current Opinion in Chemical Biology·Joseph J Braymer, David P Giedroc
Aug 28, 2014·The Journal of Biological Chemistry·Andrew W FosterNigel J Robinson
Sep 13, 2014·Molecular Microbiology·Zhen MaJohn D Helmann
Oct 14, 2014·Accounts of Chemical Research·Yue FuDavid P Giedroc
Dec 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Crysten E Blaby-HaasSabeeha S Merchant
Feb 11, 2015·Infection and Immunity·Michael D L JohnsonJason W Rosch
May 10, 2015·EMBO Reports·Daniel MattleGabriele Meloni
Jul 21, 2015·Nature Chemical Biology·Aaron T SmithAmy C Rosenzweig

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Citations

Mar 9, 2017·Journal of the American Chemical Society·Chathuri J K WijekoonZhiguang Xiao
Mar 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Daiana A CapdevilaDavid P Giedroc
Jul 29, 2016·Metallomics : Integrated Biometal Science·José M ArgüelloJulia Quintana
Oct 25, 2017·MSphere·Miranda J NeubertMichael D L Johnson
May 11, 2017·Essays in Biochemistry·Daiana A CapdevilaDavid P Giedroc
Sep 24, 2020·Membranes·Andreea AndreiHans-Georg Koch
Jan 28, 2021·FEMS Microbiology Ecology·Andrea GiachinoKevin J Waldron
Jun 3, 2021·Journal of Clinical Medicine·Gabriela Athziri Sánchez-ZunoJosé Francisco Muñoz-Valle

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