The effects of the flavonoid baicalein and osmolytes on the Mg 2+ accelerated aggregation/fibrillation of carboxymethylated bovine 1SS-alpha-lactalbumin.
Many protein conformational diseases arise when proteins form alternative stable conformations, resulting in aggregation and accumulation of the protein as fibrillar deposits, or amyloids. Interestingly, numerous proteins implicated in amyloid protein formation show similar structural and functional properties. Given this similarity, we tested the notion that carboxymethylated bovine alpha-lactalbumin (1SS-alpha-lac) could serve as a general amyloid fibrillation/aggregation model system. Like most amyloid forming systems, Mg2+ ions accelerate 1SS-alpha-lac amyloid fibril formation. While osmolytes such as trimethylamine N-oxide (TMAO), and sucrose enhanced thioflavin T detected aggregation, a mixture of trehalose and TMAO substantially inhibited aggregation. Most importantly however, the flavonoid, baicalein, known to inhibit alpha-synuclein amyloid fibril formation, also inhibits 1SS-alpha-lac amyloid with the same apparent efficacy. These data suggest that the easily obtainable 1SS-alpha-lac protein can serve as a general amyloid model and that some small molecule amyloid inhibitors may function successfully with many different amyloid systems.
Bomhoff
Greg
G
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Sloan
Kirk
K
McLain
Corey
C
Gogol
Edward P
EP
Fisher
Mark T
MT
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D000818:Animals; D002244:Carbon / Q000737:chemistry; D002417:Cattle; D019281:Dimerization; D044950:Flavanones / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry; D007768:Lactalbumin / Q000737:chemistry* / Q000648:ultrastructure*; D008274:Magnesium / Q000737:chemistry*; D008745:Methylation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure
D000682:Amyloid; D044950:Flavanones; D005419:Flavonoids; D046912:Multiprotein Complexes; C006680:baicalein; D002244:Carbon; D007768:Lactalbumin; D008274:Magnesium