2mry: Difference between revisions
No edit summary |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==NMR solution structure of copper binding protein in the apo form== | ==NMR solution structure of copper binding protein in the apo form== | ||
<StructureSection load='2mry' size='340' side='right' caption='[[2mry | <StructureSection load='2mry' size='340' side='right'caption='[[2mry]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2mry]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MRY OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[2mry]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_D39 Streptococcus pneumoniae D39]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MRY FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mry OCA], [https://pdbe.org/2mry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mry RCSB], [https://www.ebi.ac.uk/pdbsum/2mry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mry ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0M3KKS5_STRP2 A0A0M3KKS5_STRP2] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 a predicted cytoplasm-facing Cu(i) entry metal-binding site (MBS) on CopA also gives rise to a Cu-sensitivity phenotype. These findings suggest that CupA and CopA may interact and filling of the CupA S2 site with Cu(i) results in stimulation of cellular copper efflux by CopA. | |||
The S2 Cu(i) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance.,Fu Y, Bruce KE, Wu H, Giedroc DP Metallomics. 2016 Jan;8(1):61-70. doi: 10.1039/c5mt00221d. PMID:26346139<ref>PMID:26346139</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2mry" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bruce | [[Category: Large Structures]] | ||
[[Category: Fu | [[Category: Streptococcus pneumoniae D39]] | ||
[[Category: Giedroc | [[Category: Bruce K]] | ||
[[Category: Wu | [[Category: Fu Y]] | ||
[[Category: Giedroc D]] | |||
[[Category: Wu H]] | |||
Latest revision as of 09:09, 15 May 2024
NMR solution structure of copper binding protein in the apo formNMR solution structure of copper binding protein in the apo form
Structural highlights
FunctionPublication Abstract from PubMedPathogenic 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 a predicted cytoplasm-facing Cu(i) entry metal-binding site (MBS) on CopA also gives rise to a Cu-sensitivity phenotype. These findings suggest that CupA and CopA may interact and filling of the CupA S2 site with Cu(i) results in stimulation of cellular copper efflux by CopA. The S2 Cu(i) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance.,Fu Y, Bruce KE, Wu H, Giedroc DP Metallomics. 2016 Jan;8(1):61-70. doi: 10.1039/c5mt00221d. PMID:26346139[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||