Reading protein sequences backwards.
BACKGROUND
Reading a protein sequence backwards provides a new polypeptide that does not align with its parent sequence. The foldability of this new sequence is questionable. On one hand, structure prediction at low resolution using lattice simulations for such a protein provided a model close to the native parent fold or to a topological mirror image of it. On the other hand, there is no experimental evidence yet to tell whether such a retro protein folds (and to which structure) or not.


RESULTS
In this work, we have analysed the possibility of a retro protein folding in two different ways. First, we modelled the retro sequence of the alpha-spectrin SH3 domain through distance geometry and molecular dynamics. This contradicted the plausibility of a mirror image of the native domain, whereas basic considerations opposed the likelihood of the native fold. Second, we obtained experimental evidence that the retro sequences of the SH3 domain, as well as the B domain of Staphylococcal protein A and the B1 domain of Streptococcal protein G, are unfolded proteins, even though some propensities for the formation of secondary structures might remain.


CONCLUSIONS
Retro proteins are no more similar to their parent sequences than any random sequence despite their common hydrophobic/hydrophilic pattern, global amino acid composition and possible tertiary contacts. Although simple folding models contribute to our global understanding of protein folding, they cannot yet be used to predict the structure of new proteins.
Lacroix
E
E
Biostructure and Biocomputing Department, European Molecular Biology Laboratory, Heidelberg, Germany.
Viguera
A R
AR
Serrano
L
L
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D013049:Spectrin / Q000737:chemistry; D013205:Staphylococcal Protein A / Q000737:chemistry
D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; D013205:Staphylococcal Protein A; D013049:Spectrin