Reactions of denatured proteins with other cellular components to form insoluble aggregates and protection by lactoferrin.
Elucidation of the mechanism of formation of insoluble protein aggregates is essential to resolve problems such as protein folding diseases. In this study the effects of various types of biomolecules on the aggregation of denatured proteins were investigated. Denatured alpha-lactalbumin, an acidic protein, was found to be precipitated by lactoferricin, a basic peptide derived from lactoferrin. Denatured lysozyme, a basic protein, by itself showed aggregation, which was promoted by addition of native alpha-lactalbumin. Heparin and nucleic acids caused almost instant aggregation of denatured lysozyme. Native lactoferricin was also found to aggregate with heparin or nucleic acids. The results show that denatured/misfolded proteins as well as peptides are highly reactive with other cellular components to form insoluble aggregates and suggest a possible mechanism by which protein folding diseases progress. Most of the above aggregation reactions were inhibited by lactoferrin, which could form soluble complexes with denatured alpha-lactalbumin, heparin, and nucleic acids.
Takase
K
K
Department of Biotechnology, National Institute of Agrobiological Resources, Tsukuba, Ibaraki, Japan. ktakase@abr.affrc.go.jp
D006493:Heparin / Q000378:metabolism; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism*; D007781:Lactoferrin / Q000031:analogs & derivatives* / Q000378:metabolism; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation
D009696:Nucleic Acids; C082171:lactoferricin B; D006493:Heparin; D007768:Lactalbumin; D009113:Muramidase; D007781:Lactoferrin