View source for 6fn8


==Domain II of the HUMAN COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE at 1.55 A resolution==
<StructureSection load='6fn8' size='340' side='right'caption='[[6fn8]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fn8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FN8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FN8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6fn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fn8 OCA], [https://pdbe.org/6fn8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fn8 RCSB], [https://www.ebi.ac.uk/pdbsum/6fn8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fn8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CCS_HUMAN CCS_HUMAN] Delivers copper to copper zinc superoxide dismutase (SOD1).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Superoxide dismutase-1 (SOD1) maturation comprises a string of posttranslational modifications which transform the nascent peptide into a stable and active enzyme. The successive folding, metal ion binding, and disulphide acquisition steps in this pathway can be catalysed through a direct interaction with the copper chaperone for SOD1 (CCS). This process confers enzymatic activity and reduces access to noncanonical, aggregation-prone states. Here, we present the functional mechanisms of human copper chaperone for SOD1 (hCCS)-catalysed SOD1 activation based on crystal structures of reaction precursors, intermediates, and products. Molecular recognition of immature SOD1 by hCCS is driven by several interface interactions, which provide an extended surface upon which SOD1 folds. Induced-fit complexation is reliant on the structural plasticity of the immature SOD1 disulphide sub-loop, a characteristic which contributes to misfolding and aggregation in neurodegenerative disease. Complexation specifically stabilises the SOD1 disulphide sub-loop, priming it and the active site for copper transfer, while delaying disulphide formation and complex dissociation. Critically, a single destabilising amino acid substitution within the hCCS interface reduces hCCS homodimer affinity, creating a pool of hCCS available to interact with immature SOD1. hCCS substrate specificity, segregation between solvent and biological membranes, and interaction transience are direct results of this substitution. In this way, hCCS-catalysed SOD1 maturation is finessed to minimise copper wastage and reduce production of potentially toxic SOD1 species.

Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS.,Sala FA, Wright GSA, Antonyuk SV, Garratt RC, Hasnain SS PLoS Biol. 2019 Feb 8;17(2):e3000141. doi: 10.1371/journal.pbio.3000141., eCollection 2019 Feb. PMID:30735496<ref>PMID:30735496</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fn8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Antonyuk SV]]
[[Category: Garratt RC]]
[[Category: Hasnain SS]]
[[Category: Sala FA]]
[[Category: Wright GSA]]