Conformation and sequence evidence for two-fold symmetry in left-handed beta-helix fold

The left-handed beta-helix (LβH) has received interest recently as it folds as a possible solution for the structure of misfolded proteins associated with prion and Huntington's diseases. Through a combination of sequence and structure analysis, we uncover a novel feature that is common to this unique fold: a two-fold symmetry in both sequence and structure, and this feature always coupled with extended loops in the middle of the helix. Since the results reveal a two-fold symmetric pattern both in the sequence and structure, it may indicate that the symmetry in tertiary structure is coded by the symmetry in primary sequence, which agrees with Anfisen's proposal that a protein's amino-acid sequence specify its three-dimensional structure. It may also indicate that LβH adopts a two-fold repeat pattern during the evolution process and symmetry helps maintaining the stability of the helix structure. The two-fold symmetric pattern and extended loops might be important in maintaining stability of helix proteins. This discovery can be useful in understanding the folding mechanisms of this protein fold and provide insights in the relation between sequences and structures.