Designing a 20-residue protein.
Truncation and mutation of a poorly folded 39-residue peptide has produced 20-residue constructs that are >95% folded in water at physiological pH. These constructs optimize a novel fold, designated as the 'Trp-cage' motif, and are significantly more stable than any other miniprotein reported to date. Folding is cooperative and hydrophobically driven by the encapsulation of a Trp side chain in a sheath of Pro rings. As the smallest protein-like construct, Trp-cage miniproteins should provide a testing ground for both experimental studies and computational simulations of protein folding and unfolding pathways. Pro Trp interactions may be a particularly effective strategy for the a priori design of self-folding peptides.
Neidigh
Jonathan W
JW
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
Fesinmeyer
R Matthew
RM
Andersen
Niels H
NH
D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D011506:Proteins; D014364:Tryptophan