X-ray Crystallographic Structure of a Compact Dodecamer from a Peptide Derived from Aβ16-36.

The assembly of the β-amyloid peptide, Aβ, into soluble oligomers is associated with neurodegeneration in Alzheimer's disease. The Aβ oligomers are thought to be composed of β-hairpins. Here, the effect of shifting the residue pairing of the β-hairpins on the structures of the oligomers that form is explored through X-ray crystallography. Three residue pairings were investigated using constrained macrocyclic β-hairpins in which Aβ30-36 is juxtaposed with Aβ17-23, Aβ16-22, and Aβ15-21. The Aβ16-22-Aβ30-36 pairing forms a compact ball-shaped dodecamer composed of fused triangular trimers. This dodecamer may help explain the structures of the trimers and dodecamers formed by full-length Aβ.

[1]  J. Nowick,et al.  Stabilization, Assembly, and Toxicity of Trimers Derived from Aβ , 2016, Journal of the American Chemical Society.

[2]  Ewa A. Mirecka,et al.  β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor , 2016, Scientific Reports.

[3]  J. Nowick,et al.  X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin , 2016, Journal of the American Chemical Society.

[4]  J. Nowick,et al.  X-ray Crystallographic Structure of Oligomers Formed by a Toxic β-Hairpin Derived from α-Synuclein: Trimers and Higher-Order Oligomers , 2016, Journal of the American Chemical Society.

[5]  D. Eisenberg,et al.  Amyloid β-Protein C-Terminal Fragments: Formation of Cylindrins and β-Barrels. , 2016, Journal of the American Chemical Society.

[6]  K. Schulten,et al.  Transient β-hairpin formation in α-synuclein monomer revealed by coarse-grained molecular dynamics simulation. , 2015, The Journal of chemical physics.

[7]  J. Nowick,et al.  A Newcomer's Guide to Peptide Crystallography. , 2015, Israel journal of chemistry.

[8]  J. Nowick,et al.  X-ray Crystallographic Structures of Oligomers of Peptides Derived from β2-Microglobulin. , 2015, Journal of the American Chemical Society.

[9]  O. Antzutkin,et al.  A hexameric peptide barrel as building block of amyloid-β protofibrils. , 2014, Angewandte Chemie.

[10]  J. Stroud,et al.  Antiparallel Triple-strand Architecture for Prefibrillar Aβ42 Oligomers* , 2014, The Journal of Biological Chemistry.

[11]  Ewa A. Mirecka,et al.  Sequestration of a β-hairpin for control of α-synuclein aggregation. , 2014, Angewandte Chemie.

[12]  J. Nowick,et al.  X-ray Crystallographic Structures of Trimers and Higher-Order Oligomeric Assemblies of a Peptide Derived from Aβ17–36 , 2014, Journal of the American Chemical Society.

[13]  Lei Gu,et al.  Structural Insights into Aβ42 Oligomers Using Site-directed Spin Labeling*♦ , 2013, The Journal of Biological Chemistry.

[14]  Joan-Emma Shea,et al.  Role of β-hairpin formation in aggregation: the self-assembly of the amyloid-β(25-35) peptide. , 2012, Biophysical journal.

[15]  David Eisenberg,et al.  Atomic View of a Toxic Amyloid Small Oligomer , 2012, Science.

[16]  Fred H. Gage,et al.  In vivo demonstration that α-synuclein oligomers are toxic , 2011, Proceedings of the National Academy of Sciences.

[17]  Joan-Emma Shea,et al.  Human islet amyloid polypeptide monomers form ordered beta-hairpins: a possible direct amyloidogenic precursor. , 2009, Journal of the American Chemical Society.

[18]  P. Hajduk,et al.  Structural characterization of a soluble amyloid beta-peptide oligomer. , 2009, Biochemistry.

[19]  T. Härd,et al.  Stabilization of a β-hairpin in monomeric Alzheimer's amyloid-β peptide inhibits amyloid formation , 2008, Proceedings of the National Academy of Sciences.

[20]  D. Selkoe,et al.  Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers , 2006, The Journal of physiology.

[21]  M. Gallagher,et al.  A specific amyloid-β protein assembly in the brain impairs memory , 2006, Nature.

[22]  J. Nowick,et al.  A New Turn Structure for the Formation of β-Hairpins in Peptides , 2003 .