Understanding Pre-Structured Motifs (PreSMos) in Intrinsically Unfolded Proteins

Si-Hyung      Lee; Do-Hyoung      Kim; Joan      J. Han; Eun-Ji      Cha; Ji-Eun      Lim; Ye-Jin      Cho; Chewook      Lee; Kyou-Hoon      Han

doi:10.2174/138920312799277974

Abstract

Intrinsically unfolded proteins (IUPs) do not obey the golden rule of structural biology, 3D structure = function, as they manifest their inherent functions without resorting to three-dimensional structures. Absence of a compact globular topology in these proteins strongly implies that their ligand recognition processes should involve factors other than spatially well-defined binding pockets. Heteronuclear multidimensional (HetMulD) NMR spectroscopy assisted with a stable isotope labeling technology is a powerful tool for quantitatively investigating detailed structural features in IUPs. In particular, it allows us to delineate the presence and locations of pre-structured motifs (PreSMos) on a per-residue basis. PreSMos are the transient local structural elements that presage target-bound conformations and act as specificity determinants for IUP recognition by target proteins. Here, we present a brief chronicle of HetMulD NMR studies on IUPs carried out over the past two decades along with a discussion on the functional significance of PreSMos in IUPs.

Keywords: PreSMos (Pre-Structured Motifs), IUPs (Intrinsically Unfolded Proteins), NMR, IDR (Intrinsically Disordered Region), Mostly Unstructured (MU), Completely Unstructured (CU), IDPs, NUPs, Polypeptide, amphipathic helix