Proteinaceous infectious behavior in non-pathogenic proteins is controlled by molecular chaperones.
External stresses or mutations may cause labile proteins to lose their distinct native conformations and seek alternatively stable aggregated forms. Molecular chaperones that specifically act on protein aggregates were used here as a tool to address the biochemical nature of stable homo- and hetero-aggregates from non-pathogenic proteins formed by heat-stress. Confirmed by sedimentation and activity measurements, chaperones demonstrated that a single polypeptide chain can form different species of aggregates, depending on the denaturing conditions. Indicative of a cascade reaction, sub-stoichiometric amounts of one fast-aggregating protein strongly accelerated the conversion of another soluble, slow-aggregating protein into insoluble, chaperone-resistant aggregates. Chaperones strongly inhibited seed-induced protein aggregation, suggesting that they can prevent and cure proteinaceous infectious behavior in homo- and hetero-aggregates from common and disease-associated proteins in the cell.
Ben-Zvi
Anat Peres
AP
Department of Plant Sciences, A. Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Goloubinoff
Pierre
P
D000818:Animals; D002384:Catalysis; D002417:Cattle; D002498:Centrifugation; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D049071:Endopeptidase Clp; D029968:Escherichia coli Proteins / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013347:Subcellular Fractions; D013552:Swine; D013696:Temperature; D013997:Time Factors
D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; D012710:Serum Albumin, Bovine; D008291:Malate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D049071:Endopeptidase Clp; C069775:ClpB protein, E coli