Trp-cage designed protein TC5b
The design and structural characterization of miniproteins with a compact, folded structure provides insights into the protein folding and unfolding pathways including the minimum requirements for a protein sequence to fold.
In this article, a 20-residue protein that folds into a novel 'Trp-cage' motif is reported. With a poorly folded 39-residue peptide as a starting point, truncation and mutaion of the peptide has produced a 20-residue construct that is well folded in water at physiological pH. NMR measurements have shown that the Trp-cage with two proline residues on each side of the Trp indole ring plus Tyr makes up the hydrophobic core and that the Trp side-chain is 100% buried in aqueous solution. The NMR structure of the Trp-cage motif shows important features typical of a small protein. It has multiple secondary structural elements, side chain-side chain packing interactions, well defined tertiary contacts and a compact overall structure. On account of the small size, the architectural simplicity and the limited conformational flexibility, the Trp-cage miniprotein is expected to be useful for both experimental studies and computational simulations of protein folding and unfolding pathways.
Protein Data Bank (PDB)
Neidigh, J.W. Fesinmeyer, R.M. Andersen, N.H.; "Designing a 20-residue protein."; Nat.Struct.Biol.; (2002) 9:425-430 PubMed:11979279.
author: Aki Nagata