Structural Differences in Hen Egg White Lysozyme Monomers Leading to Amyloid Polymorphic Fibrils Observed by Solution X-Ray Scattering

Amyloidosis such as Alzheimer’s disease is characterized by the deposition of amyloid fibrils in organs. Amyloid fibrils show polymorphism, where the same protein forms fibrils with distinct morphologies. However, it remains unknown what structural differences in monomers result in polymorphic amyloid fibrils. Here, using small-angle X-ray scattering (SAXS) on hen egg white lysozyme, a model protein for amyloid research, monomer structures were investigated at pH 2.7 and pH 6.0, where two kinds of polymorphic amyloid fibrils are formed. It was found that the monomer takes on a highly extended conformation in the buffer to form fibrils at pH 2.7 whereas it takes on a less extended conformation in the buffer to form fibrils at pH 6.0. The resultant fibrils were found to be represented by a long cylinder with different sizes of cross-sections, suggesting polymorphic fibrillar structures. Wide-angle X-ray scattering (WAXS) measurements on the fibrils showed that both fibrils possess an inter-β-strand distance of 4.8 Å while only those at pH 6.0 possess an additional inter-β-strand distances of 4.7 Å, indicating diverse structures for this polymorph. The present results suggest that monomers with a less extended conformation hamper the formation of stable β-sheet structures, leading to diverse conformations of fibrils.