A model for the aggregation of the acylphosphatase from Sulfolobus solfataricus in its native-like state.
Evidence is accumulating that normally folded proteins retain a significant tendency to form amyloid fibrils through a direct assembly of monomers in their native-like conformation. However, the factors promoting such processes are not yet well understood. The acylphosphatase from Sulfolobus solfataricus (Sso AcP) aggregates under conditions in which a native-like state is initially populated and forms, as a first step, aggregates in which the monomers maintain their native-like topology. An unstructured N-terminal segment and an edge beta-strand were previously shown to play a major role in the process. Using kinetic experiments on a set of Sso AcP variants we shall show that the major event of the first step is the establishment of an inter-molecular interaction between the unstructured segment of one Sso AcP molecule and the globular unit of another molecule. This interaction is determined by the primary sequence of the unstructured segment and not by its physico-chemical properties. Moreover, we shall show that the conversion of these initial aggregates into amyloid-like protofibrils is an intra-molecular process in which the Sso AcP molecules undergo conformational modifications. The obtained results allow the formulation of a model for the assembly of Sso AcP into amyloid-like aggregates at a molecular level.
Bemporad
Francesco
F
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, Florence 50134, Italy.
Vannocci
Tommaso
T
Varela
Lorena
L
Azuaga
Ana I
AI
Chiti
Fabrizio
F
D017766:Acid Anhydride Hydrolases / Q000737:chemistry*; D000682:Amyloid / Q000737:chemistry*; D008958:Models, Molecular; D020836:Protein Structure, Quaternary / Q000502:physiology; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D048229:Sulfolobus solfataricus / Q000201:enzymology*; D000097024:Acylphosphatase
D017766:Acid Anhydride Hydrolases; D000682:Amyloid; D000097024:Acylphosphatase