Protein–Protein Connections—Oligomer, Amyloid and Protein Complex—By Wide Line 1H NMR

Abstract

The amount of bonds between constituting parts of a protein aggregate were determined in wild type (WT) and A53T α-synuclein (αS) oligomers, amyloids and in the complex of thymosin-β4–cytoplasmic domain of stabilin-2 (Tβ4-stabilin CTD). A53T αS aggregates have more extensive βsheet contents reflected by constant regions at low potential barriers in difference (to monomers) melting diagrams (MDs). Energies of the intermolecular interactions and of secondary structures bonds, formed during polymerization, fall into the 5.41 kJ mol−1 ≤ Ea ≤ 5.77 kJ mol−1 range for αS aggregates. Monomers lose more mobile hydration water while forming amyloids than oligomers. Part of the strong mobile hydration water–protein bonds break off and these bonding sites of the protein form intermolecular bonds in the aggregates. The new bonds connect the constituting proteins into aggregates. Amyloid–oligomer difference MD showed an overall more homogeneous solvent accessible surface of A53T αS amyloids. From the comparison of the nominal sum of the MDs of the constituting proteins to the measured MD of the Tβ4-stabilin CTD complex, the number of intermolecular bonds connecting constituent proteins into complex is 20(1) H2O/complex. The energies of these bonds are in the 5.40(3) kJ mol−1 ≤ Ea ≤ 5.70(5) kJ mol−1 range.

A Practical Guide to All-Atom and Coarse-Grained Molecular Dynamics Simulations Using Amber and Gromacs: A Case Study of Disulfide-Bond Impact on the Intrinsically Disordered Amyloid Beta

“…However, conformations of IDPs are not energetically equivalent, and transitions between them are more complicated in nature due to the larger size of proteins. Nevertheless, due to the analogy, some works are naming the behavior of some metalo- and disordered proteins as fluxional [ 6 , 7 , 8 ].…”

The Amazing World of IDPs in Human Diseases II

“…Bokor and Tantos [14] studied two different IDP interaction systems to gain information about the bonds holding the protein associations together using wide-line 1H NMR. One system consisted of wild type and mutant α-synuclein (αS) in the forms of oligomers and amyloids and the other system was the complex between the intrinsically disordered (IDP) thymosin-β4 (Tβ4) and the cytoplasmic domain of stabilin-2 (stabilin CTD), which is involved in the phagocytosis of apoptotic cells.…”