Intrinsically disordered proteins (IDP) and unfolded proteins
A large class of proteins has no defined tertiary structure. These proteins have structured parts (or not) connected by disordered regions with high degree of configurational freedom. This class challenges the traditional structure-function paradigm. The IDP's sometimes fold upon binding to an active configuration e.g. in conjunction with other molecules. Knowledge on dynamics is important to understand the structuring process prior to function, the dynamics of folding or the function as an unstructured protein itself. Two approaches can be used to elucidate the underlying phenomenon. Structured proteins can be unfolded (e.g. by temperature, pressure or chemically) to examine stable unfolded intermediates, transition regions or differences in the different unfolding mechanisms. A second approach is to observe intrinsically unfolded proteins. As an extreme case a complete unstructured protein should behave as a stiff random polymer chain [1-3]. Structure and dynamics within the unfolding process and for the unfolded protein are influenced by geometrical restrictions as remaining disulfide bonds (see animation of unfolded Ribonuclease A with 4 disulfide bonds), by charges on the amino acid strand or by stiffer regions with e.g. a preserved secondary structure.
- A. M. Stadler, L. Stingaciu, A. Radulescu, O. Holderer, M. Monkenbusch, R. Biehl, and D. Richter,
Internal Nanosecond Dynamics in the Intrinsically Disordered MyelinBasic Protein
J. Am. Chem. Soc. 136, 6987 (2014).
- F. Ameseder, A. Radulescu, M. Khaneft, W. Lohstroh, and A. M. Stadler,
Homogeneous and heterogeneous dynamics in native and denatured bovine serum albumin
Phys. Chem. Chem. Phys. 20, 5128 (2018).
- L. R. Stingaciu, R. Biehl, D. Changwoo, D. Richter, and A. M. Stadler,
Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein
J. Phys. Chem. Lett. 11, 292 (2020).