Molecular basis for amyloid fibril formation and stability.

By O. S. Makin, E. Atkins, P. Sikorski, J. Johansson, Louise C. Serpell. Proceedings of the National Academy of Sciences of the United States of America, 2005

628 citations recorded by the source corpus.

The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 A) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel beta-sheets in a cross-beta arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel beta-sheets are zipped together by means of pi-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.

Subfields: Biomaterials, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/9fef66318871e9ef3014c59de74c36356b304903

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Citations in the corpus

Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism (2006, background): “The role of aromatic interactions was recently shown to have a strong effect on amyloidogenic propensity (23) and, furthermore, recent X-ray diffraction of a short, crystallized amyloidogenic sequence revealed that aromatic interactions stabilized the anti-parallel b-sheet structure (34).”
Towards an Understanding of the Temperature/ Pressure Configurational and Free-Energy Landscape of Biomolecules (2007, positive): “Even if this is the case, fibrils are likely to play an important rule either as a reservoir or sink of toxic oligomers [113].”
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade. (2017, background): “Alternative organizations of the β-strands within fibrils are, however, found for small peptides, in which an antiparallel arrangement is sometimes preferred to a parallel one (76, 106).”
Experimental constraints on quaternary structure in Alzheimer's beta-amyloid fibrils. (2006, background): “As represented in recent models for amyloid structures (7, 10, 14, 29, 36, 42, 44, 51-59) and supported by recent x-ray crystal structures of short amyloid-forming peptides (60), the core of an amyloid fibril contains two or more layers of β-sheets.”
The FoldX web server: an online force field (2005, background): “For protein aggregation no such detail is available, although recently the ﬁrst ever crystal structure of an amyloid ﬁbre was released (23).”