title: Interaction of nonionic detergents with the specific sites of lysozyme amyloidogenic region - inhibition of amyloid fibrillization.
abstract: Two nonionic detergents, Triton X-100 (TX-100) and n-dodecyl-β-d-maltoside (DDM) were tested for their ability to affect lysozyme amyloid aggregation. We have demonstrated that fibrillization of lysozyme is completely inhibited by low sub-micellar concentrations of both of these detergents. The apparent IC50values were calculated to be 22μM and 26μM for TX-100 and DDM, respectively. The detergent/protein ratio is not the only parameter controlling inhibition. The precise timing of the detergent addition was found to be also crucial. It appears that the primary inhibitory activity of detergents resulted from inhibition of nuclei formation, in addition to inhibition of fibril polymerization at the early stage of protofibrils growth. The docking study revealed that Asn-59, Trp-63 and Ala-107, all present within the lysozyme amyloidogenic region, were involved in the interaction with both detergents. In addition, TX-100 also interacted with Gln-57 and Asp-103 within lysozyme. Moreover, based on our computational results, TX-100 bridges the Gln-57 and Ala-107 amino acids of the amyloidogenic segment of lysozyme and therefore inhibits more effectively the amyloid fibril formation. Along these lines, the knowledge gained from our study indicates that the detergents or their derivatives may be applicable as a promising strategy for the modulation of lysozyme protein aggregation.
authors.affiliation: Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia. Electronic address: katkasiposova@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Siposova
authors.affiliation: Center for multimodal imaging, Institute of Physics, Faculty of Science, P.J. Safarik University, Srobarova 2, 041 54 Kosice, Slovakia.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kozar
authors.affiliation: Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Musatov
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D052160:Benzothiazoles; D001665:Binding Sites; D002645:Chickens; D002942:Circular Dichroism; D003902:Detergents / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004529:Egg White / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008027:Light; D008823:Micelles; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry*; D017830:Octoxynol / Q000737:chemistry; D011487:Protein Conformation; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties; D013696:Temperature; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D003902:Detergents; D005960:Glucosides; D008823:Micelles; D013844:Thiazoles; C009462:thioflavin T; C040358:dodecyl maltoside; D017830:Octoxynol; D009113:Muramidase
keywords: Amyloid aggregation; Inhibition; Lysozyme; Nonionic detergent