8b9q: Difference between revisions

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-'''Unreleased structure'''
-The entry 8b9q is ON HOLD  until sometime in the future
+==Molecular structure of Cu(II)-bound amyloid-beta monomer implicated in inhibition of peptide self-assembly in Alzheimer's disease==
+<StructureSection load='8b9q' size='340' side='right'caption='[[8b9q]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8b9q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B9Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B9Q FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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=8b9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b9q OCA], [https://pdbe.org/8b9q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b9q RCSB], [https://www.ebi.ac.uk/pdbsum/8b9q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b9q ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/B4DM00_HUMAN B4DM00_HUMAN] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.[RuleBase:RU367156]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Metal ions, such as copper and zinc ions, have been shown to strongly modulate the self-assembly of the amyloid-beta (Abeta) peptide into insoluble fibrils, and elevated concentrations of metal ions have been found in amyloid plaques of Alzheimer's patients. Among the physiological transition metal ions, Cu(II) ions play an outstanding role since they can trigger production of neurotoxic reactive oxygen species. In contrast, structural insights into Cu(II) coordination of Abeta have been challenging due to the paramagnetic nature of Cu(II). Here, we employed specifically tailored paramagnetic NMR experiments to determine NMR structures of Cu(II) bound to monomeric Abeta. We found that monomeric Abeta binds Cu(II) in the N-terminus and combined with molecular dynamics simulations, we could identify two prevalent coordination modes of Cu(II). For these, we report here the NMR structures of the Cu(II)-bound Abeta complex, exhibiting heavy backbone RMSD values of 1.9 and 2.1 A, respectively. Further, applying aggregation kinetics assays, we identified the specific effect of Cu(II) binding on the Abeta nucleation process. Our results show that Cu(II) efficiently retards Abeta fibrillization by predominately reducing the rate of fibril-end elongation at substoichiometric ratios. A detailed kinetic analysis suggests that this specific effect results in enhanced Abeta oligomer generation promoted by Cu(II). These results can quantitatively be understood by Cu(II) interaction with the Abeta monomer, forming an aggregation inert complex. In fact, this mechanism is strikingly similar to other transition metal ions, suggesting a common mechanism of action of retarding Abeta self-assembly, where the metal ion binding to monomeric Abeta is a key determinant.
-Authors: Abelein, A., Ciofi-Baffoni, S., Kumar, R., Giachetti, A., Piccioli, M., Biverstal, H.
+Molecular Structure of Cu(II)-Bound Amyloid-beta Monomer Implicated in Inhibition of Peptide Self-Assembly in Alzheimer's Disease.,Abelein A, Ciofi-Baffoni S, Morman C, Kumar R, Giachetti A, Piccioli M, Biverstal H JACS Au. 2022 Nov 11;2(11):2571-2584. doi: 10.1021/jacsau.2c00438. eCollection , 2022 Nov 28. PMID:36465548<ref>PMID:36465548</ref>
-Description: Molecular structure of Cu(II)-bound amyloid-beta monomer implicated in inhibition of peptide self-assembly in Alzheimer''s disease
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Biverstal, H]]
+<div class="pdbe-citations 8b9q" style="background-color:#fffaf0;"></div>
-[[Category: Kumar, R]]
+== References ==
-[[Category: Ciofi-Baffoni, S]]
+<references/>
-[[Category: Piccioli, M]]
+__TOC__
-[[Category: Giachetti, A]]
+</StructureSection>
-[[Category: Abelein, A]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Abelein A]]
+[[Category: Biverstal H]]
+[[Category: Ciofi-Baffoni S]]
+[[Category: Giachetti A]]
+[[Category: Kumar R]]
+[[Category: Piccioli M]]