Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana.
AtFKBP13, an immunophilin in the chloroplast thylakoid lumen, participates in redox-regulatory processes via a pair of conserved disulfide bonds that are present at the N- and C-termini of the protein. Characterization of this protein by structural and biochemical analysis has revealed a novel mechanism of redox regulation in the thylakoid lumen. The protein is active in its oxidized form but is inactivated after reduction by the thioredoxin system. This is in sharp contrast with the regulation of biosynthetic enzymes in the stroma of the chloroplast, where reduction of enzymes by thioredoxin activates their function. To understand how the reduced form of AtFKBP13 is stabilized and how reduction of the cysteine residues affects the molecular properties of the enzyme, we determined the crystal structure of reduced AtFKBP13 at 1.88 A. Comparison of the reduced structure and the oxidized form that we published earlier shows rearrangements in redox site regions, readjustments of hydrogen-bonding interactions and the secondary structure of the active site residues 50-53, and reduced accessibility of the catalytic residues involved in the peptidyl proline isomerase (PPIase) activity of this enzyme. We propose that redox-linked changes in the secondary structure of the PPIase domain are responsible for significant functional differences in this protein in the reduced and oxidized states.
Gopalan
Gayathri
G
Department of Biological Sciences, National University of Singapore, Singapore.
He
Zengyong
Z
Battaile
Kevin P
KP
Luan
Sheng
S
Swaminathan
Kunchithapadam
K
D029681:Arabidopsis Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D022021:Tacrolimus Binding Proteins / Q000737:chemistry*
D029681:Arabidopsis Proteins; C517220:FKBP13 protein, Arabidopsis; D011994:Recombinant Proteins; C070133:FKBP-13; D022021:Tacrolimus Binding Proteins