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of outstanding interest Gassner NC, Baase WA, Matthews BW. A test of the 'jigsaw puzzle' model for protein folding by multiple methionine substitutions within the core of T4 lysozyme. Proc Natl Acad Sci USA. 93:1996;12155-12158 This crystallographic and thermodynamic study of T4 lysozyme variants with significantly simplified hydrophobic cores demonstrates clearly the extraordinary degree of core compositional simplicity that a globular protein can accommodate and poses a serious challenge to the 'jigsaw puzzle' model of core packing and protein structure.
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of outstanding interest. A phage display technique was used to select for significantly simplified proteins that adopt an SH3 domain fold. These studies suggest that a five-letter alphabet is the minimal compositional complexity required to generate this predominantly β-sheet fold. The rapid folding of the highly simplified variants recovered in this work (one folds 50% more rapidly than the wild-type sequence from which it was derived) suggests that sequence complexity of naturally occurring proteins is not required to generate rapidly folding species.
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of outstanding interest Riddle DS, Santiago JV, Bray ST, Doshi N, Grantcharova V, Yi Q, Baker D. Functional rapidly folding proteins from simplified amino acid sequences. Nat Struct Biol. 4:1997;805-809 A phage display technique was used to select for significantly simplified proteins that adopt an SH3 domain fold. These studies suggest that a five-letter alphabet is the minimal compositional complexity required to generate this predominantly β-sheet fold. The rapid folding of the highly simplified variants recovered in this work (one folds 50% more rapidly than the wild-type sequence from which it was derived) suggests that sequence complexity of naturally occurring proteins is not required to generate rapidly folding species.
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of outstanding interest Munson M, Anderson KS, Regan L. Speeding up protein folding: mutations that increase the rate at which Rop folds and unfolds by over four orders of magnitude. Fold Des. 2:1997;77-87 This investigation into the folding rates of core-simplified variants of Rop suggests that the potential packing redundancy of simplified hydrophobic cores does not reduce protein folding rates. Indeed, all of the simplified variants investigated fold more rapidly than the wild-type sequence from which they were derived, potentially due to the removal of buried hydrophilic residues.
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of outstanding interest. This crystallographic study of a de novo designed, seven-residue type, 108 residue, four-helix bundle clearly demonstrates that only limited compositional and pattern complexity are required to generate truly native proteins
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