Structure of the cross-β spine of amyloid-like fibrils

Structure of the cross-β spine of amyloid-like fibrils

2005 June 9; 435(7043): 773–778 | Rebecca Nelson, Michael R. Sawaya, Melinda Balbirnie, Anders Ø. Madsen, Christian Riek, Robert Grothe, and David Eisenberg
The article by Nelson et al. (2006) investigates the atomic structure of the cross-β spine in amyloid-like fibrils, focusing on a seven-residue peptide segment from the yeast protein Sup35. The peptide, GNNQQNY, forms amyloid-like fibrils and microcrystals, which are used to reveal the structure of the cross-β spine. The spine is composed of two parallel β-sheets stacked in-register, with sidechains forming a self-complementing steric zipper that binds the sheets together. Each sheet is stabilized by stacks of backbone and sidechain hydrogen bonds, and the dry interface between the sheets is highly complementary, with sidechains interdigitating to form van der Waals interactions. The structure suggests that the stable unit of the cross-β spine is a pair of β-sheets, which may explain the self-limiting lateral growth of fibrils and their tendency to form polymorphic structures. The study also discusses the energetic barriers to fibril formation and the role of protein concentration in this process. The findings provide insights into the stability and self-seeding characteristics of amyloid fibrils, which are associated with fatal diseases such as Alzheimer's.The article by Nelson et al. (2006) investigates the atomic structure of the cross-β spine in amyloid-like fibrils, focusing on a seven-residue peptide segment from the yeast protein Sup35. The peptide, GNNQQNY, forms amyloid-like fibrils and microcrystals, which are used to reveal the structure of the cross-β spine. The spine is composed of two parallel β-sheets stacked in-register, with sidechains forming a self-complementing steric zipper that binds the sheets together. Each sheet is stabilized by stacks of backbone and sidechain hydrogen bonds, and the dry interface between the sheets is highly complementary, with sidechains interdigitating to form van der Waals interactions. The structure suggests that the stable unit of the cross-β spine is a pair of β-sheets, which may explain the self-limiting lateral growth of fibrils and their tendency to form polymorphic structures. The study also discusses the energetic barriers to fibril formation and the role of protein concentration in this process. The findings provide insights into the stability and self-seeding characteristics of amyloid fibrils, which are associated with fatal diseases such as Alzheimer's.
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[slides and audio] Structure of the cross-%CE%B2 spine of amyloid-like fibrils