Pro ( 26 ) Ala single - site mutation observed in the crystal structure of Fis mutant Conversion of a { beta } - strand to an { alpha } - helix induced

The conversion from an a-helix to a P-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 P-strand to an a-helix by a single-site mutation as observed in the crystal structure of Fis mutant Pro26Ala determined at 2.0 8, resolution. Pro26 in Fis occurs at the point where a flexible extended P-hairpin arm leaves the core structure. Thus it can be classified as a “hinge proline” located at the C-terminal end of the P2-strand and the N-terminal cap of the A a-helix. The replacement of Pro26 to alanine extends the A a-helix for two additional turns in one of the dimeric subunits; therefore, the structure of the peptide from residues 22 to 26 is converted from a P-strand to an a-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 P-strand conformation in the crystal; therefore, this peptide shows a “chameleon-like’’ character since it can adopt either an a-helix or a P-strand structure in different environments. The structure of Pro26Ala provides an additional example where not only the protein sequence, but also non-local interactions determine the secondary structure of proteins.