Natural β-sheet proteins use negative design to avoid edge-to-edge aggregation

By Jane S. Richardson, David C Richardson. Proceedings of the National Academy of Sciences of the United States of America, 2002

782 citations recorded by the source corpus.

Subfields: Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e2e0236ef7ea8e5b67eccc2ed58adc9c92f06db0

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Citations in the corpus

Local Protein Structures (2007, background): “9 they play an important role in protein–protein interaction and in protein function [93, 94] and have been suggested to be associated with some pathologies, like the aggregation of proteins into a fibrillar structure in the case of several neurodegenerative disorders [95].”
Molecular Mechanism of Thioflavin-T Binding to Amyloid Fibrils (2010, background): “Typical globular proteins contain highly twisted β-sheets consisting of less than four β-strands, which are thus too distorted and too short to form suitable ThT-binding motifs [38,51,52].”
De novo protein design, a retrospective (2020, background): “As mentioned above, Dahiyat and Mayo had also succeeded in the fully automated redesign of the sequence of a zinc finger peptide, resulting in a peptide that folded into a structure consisting of an α-helix packed against an antiparallel β-hairpin (Richardson and Richardson, 2002).”
The highly cooperative folding of small naturally occurring proteins is likely the result of natural selection. (2007, background): “In addition, edge strands of naturally occurring proteins may be selected to inhibit nonspecific intermolecular interactions across b sheet interfaces (Richardson and Richardson, 2002) and this may also be true for intramolecular interactions involving b strands.”
A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins. (2003, methodology): “20 Since designing a kink in any strand would change the redesign backbone from its native target, we are testing the feasibility of the second anti-aggregation strategy by constructing variants of redesigned tenascin and FKBP12 that replace edge-strand partially surface-exposed hydrophobic…”
Computational design of a symmetric homodimer using β-strand assembly (2011, background): “Protecting elements, typical of exposed strands in monomeric proteins, are less prevalent at β -strand mediated protein interfaces (17, 25).”