Conversion of a β‐strand to anα‐helix induced by a single‐site mutation observed in the crystal structure of fis mutant pro 26 Ala

The conversion from anα‐helix to a β‐strand has received extensive attention since this structural change may induce many amyloidogenic proteins to self‐assemble into fibrils and cause fatal diseases. Here we report the conversion of a peptide segment from a β‐strand to anα‐helix by a single‐site mutation as observed in the crystal structure of Fis mutant Pro 26 Ala determined at 2.0 Å resolution. Pro 26 in Fis occurs at the point where a flexible extended β‐hairpin arm leaves the core structure. Thus it can be classified as a “hinge proline” located at the C‐terminal end of the β2‐strand and the N‐terminal cap of the Aα‐helix. The replacement of Pro 26 to alanine extends the Aα‐helix for two additional turns in one of the dimeric subunits; therefore, the structure of the peptide from residues 22 to 26 is converted fromα β‐strand to anα‐helix. This result confirms the structural importance of the proline residue located at the hinge region and may explain the mutant's reduced ability to activate Hin‐catalyzed DNA inversion. The peptide (residues 20 to 26) in the second monomer subunit presumably retains its β‐strand conformation in the crystal; therefore, this peptide shows a “chameleon‐like” character since it can adopt either anα‐helix or a β‐strand structure in different environments. The structure of Pro 26 Ala provides an additional example where not only the protein sequence, but also non‐local interactions determine the secondary structure of proteins.