6vu4: Difference between revisions
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The | ==Structure of a beta-hairpin peptide mimic derived from Abeta 14-36== | ||
<StructureSection load='6vu4' size='340' side='right'caption='[[6vu4]], [[Resolution|resolution]] 2.08Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6vu4]] 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=6VU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VU4 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]] 2.077Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</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=6vu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vu4 OCA], [https://pdbe.org/6vu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vu4 RCSB], [https://www.ebi.ac.uk/pdbsum/6vu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vu4 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic beta-hairpin peptides derived from the central and C-terminal regions of Abeta, which bear "tails" derived from the N-terminus of Abeta. Soluble oligomers of the beta-amyloid peptide, Abeta, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of Abeta as a region that may initiate the formation of damaging oligomeric species. Our laboratory has previously studied macrocyclic beta-hairpin peptides derived from Abeta16-22 and Abeta30-36, capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length Abeta, we use an orthogonal protecting group strategy during the synthesis to append residues from Abeta1-14 to the parent macrocyclic beta not-hairpin peptide 1, which comprises Abeta16-22 and Abeta30-36. The N-terminally extended peptides N+1, N+2, N+4, N+6, N+8, N+10, N+12, and N+14 assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide N+1 assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of Abeta oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of Abeta accommodated by the oligomers as an unstructured tail. | |||
Effects of N-Terminal Residues on the Assembly of Constrained beta-Hairpin Peptides Derived from Abeta.,Samdin TD, Wierzbicki M, Kreutzer AG, Howitz WJ, Valenzuela M, Smith A, Sahrai V, Truex NL, Klun M, Nowick JS J Am Chem Soc. 2020 Jun 5. doi: 10.1021/jacs.0c05186. PMID:32501687<ref>PMID:32501687</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6vu4" style="background-color:#fffaf0;"></div> | ||
[[Category: Nowick | == References == | ||
[[Category: Samdin | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Kreutzer A]] | |||
[[Category: Nowick JS]] | |||
[[Category: Samdin T]] | |||
[[Category: Wierzbicki M]] | |||
Latest revision as of 11:20, 11 October 2023
Structure of a beta-hairpin peptide mimic derived from Abeta 14-36Structure of a beta-hairpin peptide mimic derived from Abeta 14-36
Structural highlights
Publication Abstract from PubMedThis paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic beta-hairpin peptides derived from the central and C-terminal regions of Abeta, which bear "tails" derived from the N-terminus of Abeta. Soluble oligomers of the beta-amyloid peptide, Abeta, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of Abeta as a region that may initiate the formation of damaging oligomeric species. Our laboratory has previously studied macrocyclic beta-hairpin peptides derived from Abeta16-22 and Abeta30-36, capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length Abeta, we use an orthogonal protecting group strategy during the synthesis to append residues from Abeta1-14 to the parent macrocyclic beta not-hairpin peptide 1, which comprises Abeta16-22 and Abeta30-36. The N-terminally extended peptides N+1, N+2, N+4, N+6, N+8, N+10, N+12, and N+14 assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide N+1 assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of Abeta oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of Abeta accommodated by the oligomers as an unstructured tail. Effects of N-Terminal Residues on the Assembly of Constrained beta-Hairpin Peptides Derived from Abeta.,Samdin TD, Wierzbicki M, Kreutzer AG, Howitz WJ, Valenzuela M, Smith A, Sahrai V, Truex NL, Klun M, Nowick JS J Am Chem Soc. 2020 Jun 5. doi: 10.1021/jacs.0c05186. PMID:32501687[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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