Plant defensins (PDs), disintegrins, among other classes of small proteins highly cross-linked by disulfide bonds, lack a canonical hydrophobic core. They display almost all hydrophobic residues on the protein surface. The exposed hydrophobic residues form surface clusters stabilized by the vicinity of hydrophilic residues and the hydration shell. Despite the cysteine disulfide stabilization, they are highly dynamic. We studied the dynamics of a plant defensin Psd2 (1), Sd5 (2) and the disintegrin jarastatin (rJast) (3, 4) as models to study the formation and stabilization of the local foldons named surface hydrophobic clusters (SHC). Using the temperature dependence of 15N CPMG relaxation dispersion profiles we described the complex dynamics of these proteins and propose that the dynamics is correlated by the presence of the local foldons, since there is correlation between residues undergoing conformational exchange and the SHCs. The foldons are stabilized by solvent-induced hydrophobic forces and can be cold-destabilized. For the disintegrin rJast, we showed the presence of conformational plasticity all along the protein and constructed a model of interaction with the integrin aVb3 based on NMR-derived intermolecular restraints. The interaction demands the plasticity provided by rJast dynamics. The NMR model gives insights on the mechanism of action of disintegrins.
Acknowledgement: FAPERJ, CNPq, Capes.