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| | ==Structure of module 2 from the E1 domain of C. elegans APL-1== | | ==Structure of module 2 from the E1 domain of C. elegans APL-1== |
| - | <StructureSection load='2m05' size='340' side='right'caption='[[2m05]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m05' size='340' side='right'caption='[[2m05]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m05]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caeel Caeel]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M05 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m05]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M05 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">apl-1, C42D8.8 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2m05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m05 OCA], [https://pdbe.org/2m05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m05 RCSB], [https://www.ebi.ac.uk/pdbsum/2m05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m05 ProSAT]</span></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=2m05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m05 OCA], [https://pdbe.org/2m05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m05 RCSB], [https://www.ebi.ac.uk/pdbsum/2m05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m05 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A4_CAEEL A4_CAEEL] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hinds, M G]] | + | [[Category: Hinds MG]] |
| - | [[Category: Leong, S]] | + | [[Category: Leong S]] |
| - | [[Category: Amyloid precursor protein]]
| + | |
| - | [[Category: Apl-1]]
| + | |
| - | [[Category: Unknown function]]
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| Structural highlights
Function
A4_CAEEL
Publication Abstract from PubMed
Aberrant regulation of transition metals and the resultant disregulation of neuronal reactive oxygen species (ROS) are considered significant in the etiology of Alzheimer's disease (AD). We determined the solution structure of the D2 domain of APL-1 (APL1-D2), the Caenorhabditis elegans ortholog of the amyloid precursor protein domain 2 (APP-D2). The copper binding affinities of APL1-D2 and APP-D2 were estimated and the ability of their copper complexes to promote formation of ROS was tested. The two protein domains are isostructural, consisting of a three-stranded beta-sheet packed against a short alpha-helix in a betaalphabetabeta fold. A six-residue insert in APL1-D2, absent in APP-D2, forms an extended loop. The putative copper binding ligands in APP-D2 are not conserved in APL1-D2 and this delineates a clear difference between them. APL1-D2 and APP-D2 bind one equivalent of Cu(i) weakly, with dissociation constants KD approximately 10(-8.6) M and approximately 10(-10) M, respectively, and up to two equivalents of Cu(ii) with KD values in the range 10(-6) -10(-8) M. The relative abilities of APL1-D2, APP-D2 and amyloid-beta (Abeta) copper complexes to generate H2O2 correspond to their copper binding affinities. Copper affinities for Abeta (KD approximately 10(-10) M for both Cu(i) and Cu(ii)) and APP-D2 are in a range allowing redox cycling to occur, albeit less efficiently for APP-D2. However, APL1-D2 binds Cu(i) and Cu(ii) too weakly to sustain catalysis which further suggests that it plays no significant role in copper handling in C. elegans. Overall, the data are consistent with a possible role in copper homeostasis for APP-D2, but not APL1-D2.
Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function.,Leong SL, Young TR, Barnham KJ, Wedd AG, Hinds MG, Xiao Z, Cappai R Metallomics. 2013 Dec 18;6(1):105-16. doi: 10.1039/c3mt00258f. PMID:24276282[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leong SL, Young TR, Barnham KJ, Wedd AG, Hinds MG, Xiao Z, Cappai R. Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function. Metallomics. 2013 Dec 18;6(1):105-16. doi: 10.1039/c3mt00258f. PMID:24276282 doi:http://dx.doi.org/10.1039/c3mt00258f
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