CONVERSION OF A BETA-STRAND TO AN ALPHA-HELIX INDUCED BY A SINGLE-SITE MUTATION OBSERVED IN THE CRYSTAL-STRUCTURE OF FIS MUTANT PRO(26)ALA

Citation
Wz. Yang et al., CONVERSION OF A BETA-STRAND TO AN ALPHA-HELIX INDUCED BY A SINGLE-SITE MUTATION OBSERVED IN THE CRYSTAL-STRUCTURE OF FIS MUTANT PRO(26)ALA, Protein science, 7(9), 1998, pp. 1875-1883
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
Journal title
ISSN journal
0961-8368
Volume
7
Issue
9
Year of publication
1998
Pages
1875 - 1883
Database
ISI
SICI code
0961-8368(1998)7:9<1875:COABTA>2.0.ZU;2-A
Abstract
The conversion from an alpha-helix to a beta-strand has received exten sive attention since this structural change may induce many amyloidoge nic proteins to self-assemble into fibrils and cause fatal diseases. H ere we report the conversion of a peptide segment from a beta-strand t o an alpha-helix by a single-site mutation as observed in the crystal structure of Fis mutant Pro(26)Ala determined at 2.0 Angstrom resoluti on. Pro(26) 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 beta 2-strand a nd the N-terminal cap of the A alpha-helix. The replacement of Pro(26) 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. T his result confirms the structural importance of the proline residue l ocated at the hinge region and may explain the mutant's reduced abilit y 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 ''chamele on-like'' character since it can adopt either an alpha-helix or a beta -strand structure in different environments. The structure of Pro(26)A la provides an additional example where not only the protein sequence, but also non-local interactions determine the secondary structure of proteins.