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==X-ray crystallographic structure of an Abeta 17-36 beta-hairpin. LV(PHI)FAEDCGSNKCAII(SAR)L(ORN)V== | |||
<StructureSection load='5how' size='340' side='right' caption='[[5how]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5how]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HOW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HOW FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hox|5hox]], [[5hoy|5hoy]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5how FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5how OCA], [http://pdbe.org/5how PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5how RCSB], [http://www.ebi.ac.uk/pdbsum/5how PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
High-resolution structures of oligomers formed by the beta-amyloid peptide Abeta are needed to understand the molecular basis of Alzheimer's disease and develop therapies. This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Abeta. The development of a peptide in which Abeta17-36 is stabilized as a beta-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported. Two covalent constraints act in tandem to stabilize the Abeta17-36 peptide in a hairpin conformation: a delta-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29. An N-methyl group at position 33 blocks uncontrolled aggregation. The peptide readily crystallizes as a folded beta-hairpin, which assembles hierarchically in the crystal lattice. Three beta-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore. This hierarchical assembly provides a model, in which full-length Abeta transitions from an unfolded monomer to a folded beta-hairpin, which assembles to form oligomers that further pack to form an annular pore. This model may provide a better understanding of the molecular basis of Alzheimer's disease at atomic resolution. | |||
X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Abeta17-36 beta-Hairpin.,Kreutzer AG, Hamza IL, Spencer RK, Nowick JS J Am Chem Soc. 2016 Apr 6;138(13):4634-42. doi: 10.1021/jacs.6b01332. Epub 2016, Mar 29. PMID:26967810<ref>PMID:26967810</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Nowick, J | <div class="pdbe-citations 5how" style="background-color:#fffaf0;"></div> | ||
[[Category: Spencer, R | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Kreutzer, A G]] | |||
[[Category: Nowick, J S]] | |||
[[Category: Spencer, R K]] | |||
[[Category: Alzheimers']] | |||
[[Category: Amyloid]] | |||
[[Category: Beta-hairpin]] | |||
[[Category: Oligomer]] | |||
[[Category: Protein fibril]] | |||