Conserved structural and dynamics features in the denatured states of drosophila SUMO, human SUMO and ubiquitin proteins: implications to sequence-folding paradigm

Abstract

We have characterized here the structural and dynamics properties of urea-denatured state of dSmt3 by multidimensional NMR at 27°C and pH 5.6. The various results suggest that hydrophobic clusters as well as different native and non-native secondary structural elements are transiently formed. The backbone in the regions Gln26-Lys31 and Gly47-Gln60 shows conformationally restricted motions. The AABUF profile of the sequence reflected that this region has the highest tendency to undergo hydrophobic clustering and may thus assist the formation of transient structures. The secondary chemical shifts and coupling constants indicated that this region has strong tendency to occupy the broad β-domain of (Φ,ψ) space. A number of NMR parameters indicated that the region Asp58-Gln60 (corresponding to β3-β4 turn in the folded state) has residual turn-like structure. The present structural and dynamics results on urea-denatured dSmt3 have been compared with the previously published results on denatured states of similar fold proteins e.g. human SUMO-1 (55% homologous), ubiquitin (13.8% homologous) and GB1. Although the sequence homology is rather poor between them, the residual structure in all cases seems to be largely native type. The implications of these to sequence-folding paradigm and initial folding processes have been discussed.