Conversion of a
beta-strand to an alpha-helix induced by a single-site mutation observed in the
crystal structure of Fis mutant Pro26Ala
WEI-ZEN
YANG, TZU-PING KO, LEAH CORSELLI, REID C. JOHNSON,
and HANNA S. YUAN
Abstract
The conversion from an alpha-helix to a
beta-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
beta-strand to an alpha-helix by a single-site mutation as observed in the
crystal structure of Fis mutant Pro26Ala determined at 2.0 Å resolution.
Pro26 in Fis occurs at the point where a flexible extended beta-hairpin arm
leaves the core structure. Thus it can be classified as a "hinge
proline" located at the C-terminal end of the beta2-strand and the
N-terminal cap of the A alpha-helix. The replacement of Pro26 to alanine
extends the A alpha-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 beta-strand to an alpha-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 beta-strand conformation in the crystal; therefore, this peptide shows a
"chameleon-like" character since it can adopt either an alpha-helix
or a beta-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.
Keywords: conformational change; hinge proline; secondary
structural change; X-ray diffraction
Protein Science,
7:1875-1883, 1998
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