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Structural plasticity of peptidyl-prolyl isomerase sFkpA is a key to its chaperone function as revealed by solution NMR.

Hu K, Galius V, Pervushin K

Laboratorium für Physikalische Chemie, ETH-Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland. hukaifeng@niddk.nih.gov

Intramolecular dynamics of periplasmic chaperone FkpA-deltaCT (sFkpA) and its complexes with partially structured substrates are studied by NMR in solution. The backbone amide 15N relaxation of sFkpA reveals flexibility in the relative orientation between the dimerization domain and two juxtaposed catalytic domains identified in the X-ray structure of sFkpA. This flexibility is attributed to the structural plasticity within the long alpha-helical arm (helix III) consisting of residues 84 and 91. Residual dipolar couplings (RDCs) indicate an absence of fixed orientation between the sFkpA domains. The substrate binding surface of sFkpA is defined on the X-ray structure by mapping of chemical shift perturbations introduced by complexation of sFkpA with its corresponding protein substrates: partially folded RNase A S-protein and reduced carboxymethylated bovine alpha-lactalbumin (RCM-la). A comparison of 15N relaxation of apo-sFkpA and its complex with RNase A S-protein indicates an increased rigidity within the long alpha-helix III and decreased interdomain mobility of the complex. We speculate that these dynamic properties may play a key role in the chaperone activity of sFkpA, since ability to bind different substrates potentially requires structural adaptations of the chaperone protein. We show that binding of sFkpA to RNase A S-protein greatly reduces the population of aggregated oligomeric species of RNase A S-protein. Finally, a molecular model, the so-called "mother's arms" model, is proposed to illustrate the mechanism of chaperone activity by FkpA.

Published 27 September 2006 in Biochemistry, 45(39): 11983-91.
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