“Native-like aggregation” of the acylphosphatase from Sulfolobus solfataricus and its biological implications

Abstract 

Studies in vitro show that globular proteins can experience the formation of native-like conformational states able to self-assemble with no need of transitions across the energy barrier for unfolding, and that such processes can lead eventually to the formation of amyloid-like species. Circumstantial evidence collected in vivo suggests that aggregation of native-like states can be a concrete possibility for living organisms and thus more relevant than previously thought. In this review we summarize the key observations collected on the “native-like aggregation” of the acylphosphatase from Sulfolobus solfataricus, a protein that has allowed the direct monitoring and analysis of native-like aggregates for its propensity to form rapidly native-like aggregates and their slow conversion into amyloid-like aggregates.

Abbreviations: AcPDro2, second acylphosphatase from Drosophila melanogaster, ANS, 8-anilino-1-naphthalenesulfonate, CD, circular dichroism, CR, Congo red, ΔN11 Sso AcP, mutant of Sso AcP lacking the initial 11 residues, FTIR, Fourier transform infrared spectroscopy, N, native state, N^∗, native-like state, N11, peptide corresponding to the initial 11 residues of the Sso AcP sequence, N14, peptide corresponding to the initial 14 residues of the Sso AcP sequence, Sso AcP, acylphosphatase from Sulfolobus solfataricus, TFE, 2,2,2-trifluoroethanol, ThT, Thioflavin T, TTR, transthyretin

Keywords: Self-assembly, Protofibril, Inclusion body, Flexibility