Does a backwardly read protein sequence have a unique native state?

• Published in: Protein engineering 1996-01, Vol.9 (1), p.5-14
• Main Authors: Olszewski, Krzysztof A., Kolinski, Andrzej, Skolnick, Jeffrey
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Computer Simulation; lattice representation of proteins; Models, Molecular; Molecular Sequence Data; Monte Carlo Method; Protein Conformation; Protein Engineering; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; retro-protein A; Staphylococcal protein A; Staphylococcal Protein A - chemistry; three-helix bundle
• ISSN: 1741-0126; 0269-2139; 1741-0134
• DOI: 10.1093/protein/9.1.5

Amino acid sequences of native proteins are generally not palindromic. Nevertheless, the protein molecule obtained as a result of reading the sequence backwards, i.e. a retro-protein, obviously has the same amino acid composition and the same hydrophobicity profile as the native sequence. The important questions which arise in the context of retro-proteins are: does a retro-protein fold to a well defined native-like structure as natural proteins do and, if the answer is positive, does a retro-protein fold to a structure similar to the native conformation of the original protein? In this work, the fold of retro-protein A, originated from the retro-sequence of the B domain of Staphylococcal protein A, was studied. As a result of lattice model simulations, it is conjectured that the retro-protein A also forms a three-helix bundle structure in solution. It is also predicted that the topology of the retro-protein A three-helix bundle is that of the native protein A, rather than that corresponding to the mirror image of native protein A. Secondary structure elements in the retro-protein do not exactly match their counterparts in the original protein structure; however, the amino acid side chain contact pattern of the hydrophobic core is partly conserved.