POSSIBLE PATHWAYS OF AMYLOID FIBRIL
FORMATION ON THE EXAMPLE OF INSULIN PROTEIN
Соколович О.А., студ., Дорошевич А.К., студ.,
Саган В.В., студ.
Международный государственный экологический институт
имени А. Д. Сахарова, филиал БГУ,
Минск, Республика Беларусь
Научный руководитель: Богданова Н.В., ст. преп.
Research of the structure of ordered protein aggregates — amyloid
fibrils, the influence of the native protein structure and external conditions
on the process of fibrillation a very important topic for research nowadays.
The formation of various structures by the prion mechanism is convincing
proof. This show how one protein can form various structures, including
amyloids and amyloid-like fibrils, due to changes in conformation.
Especially it became relevant when it turned out that improper folding
of some proteins can cause pathological aggregations and lead to the
development of many neurodegenerative diseases, such as Alzheimer's
disease and Parkinson's disease, T2DM etc. But it should be noted that
not all amyloids and various amyloid-like fibrils are associated with
neurodegenerative diseases, and this property is inherent in many proteins.
Although, despite such a variety of proteins, the amyloid fibrils, that formed
are similar to each other at first blush and represent stacked antiparallel
β-structures directed perpendicular to the fibril axis. Amyloid fibrils can
be straight or twisted, it can contain many protofilaments that line up
parallel to the fibril axis or twist relatively to each other. It can be imagined
that amyloid fibrils are antiparallel β-sheets twisted into a spiral; a cavity is
formed inside the spiral, like a cylinder.
An important difference between protein folding into a native structure
and the formation of amyloid fibrils is that when folding into a native
structure, a correspondence between the amino acid sequence and
the uniqueness of the folded state is assumed, whereas during amyloid
formation, the same polypeptide sequence can form fibrils of different
morphologies. Currently we can distinguish three ways of the formation
of amyloid fibrils depending on the nucleus size. The first suggests that
580
ЭКСПЕРИМЕНТАЛЬНАЯ И КЛИНИЧЕСКАЯ ПАТОФИЗИОЛОГИЯ
fibrillogenesis can occur through assembly of insulin monomers. The
second assumed that precursors of fibrils are dimers. The third suggests
that precursors of fibrils are oligomers.
Research of the identities of the formation of amyloid fibrils based on
insulin may be of significant importance for the improvement of insulin
therapy in patients with diabetes mellitus.
ЭКСПЕРИМЕНТАЛЬНАЯ И КЛИНИЧЕСКАЯ ПАТОФИЗИОЛОГИЯ
581
Do'stlaringiz bilan baham: |