Insoluble amyloid fibrils formed by self-assembly of amyloidogenic regions of proteins have a cross-β-structure. In this work, by using targeted molecular dynamics and rigid body simulation, we demonstrate that if a protein consists of an amyloidogenic region and a globular domain(s) and if the linker between them is short enough, such molecules cannot assemble into amyloid fibrils, instead, they form oligomers with a defined and limited number of β-strands in the cross-β core. We show that this blockage of the amyloid growth is due to the steric repulsion of the globular structures linked to amyloidogenic regions. Furthermore, we establish a relationship between the linker length and the number of monomers in such nanoparticles. We hypothesise that such oligomerisation can be a yet unrecognised way to form natural protein complexes involved in biological processes. Our results can also be used in protein engineering for designing soluble nanoparticles carrying different functional domains.
Предметные области OECD FOS+WOS
- 1.06.CQ БИОХИМИЯ И МОЛЕКУЛЯРНАЯ БИОЛОГИЯ
- 1.06.DA БИОФИЗИКА
- 1.06.DR КЛЕТОЧНАЯ БИОЛОГИЯ