Biochemistry (Moscow)

, Volume 77, Issue 11, pp 1237–1247

Structural polymorphism and possible pathways of amyloid fibril formation on the example of insulin protein

Authors

  • O. M. Selivanova
    • Institute of Protein ResearchRussian Academy of Sciences
    • Institute of Protein ResearchRussian Academy of Sciences
Review

DOI: 10.1134/S0006297912110028

Cite this article as:
Selivanova, O.M. & Galzitskaya, O.V. Biochemistry Moscow (2012) 77: 1237. doi:10.1134/S0006297912110028

Abstract

In this review we analyze the main works on amyloid formation of insulin. There are many environmental factors affecting the formation of insulin amyloid fibrils (and other amyloidogenic proteins) such as: protein concentration, pH, ionic strength of solution, medium composition (anions, cations), presence of denaturants (urea, guanidine chloride) or stabilizers (saccharose), temperature regime, agitation. Since polymorphism is potentially crucial for human diseases and may underlie the natural variability of some amyloid diseases, in this review we focus attention on polymorphism that is an important biophysical difference between native protein folding suggesting correspondence between the amino acid sequence and unique folding state, and formation of amyloid fibrils, when the same amino acid sequence can form amyloid fibrils of different morphology. At present, according to the literature data, we can choose three ways of polymerization of insulin molecules depending on the nucleus size. The first suggests that fibrillogenesis can occur through assembly of insulin monomers. The second suggests that precursors of fibrils are dimers, and the third assumes that precursors of fibrils are oligomers. Additional experimental works and new methods of investigation and assessment of results are needed to clarify the general picture of insulin amyloid formation.

Key words

amyloid fibrilprotofibriloligomernucleusinsulininjection amyloidosis

Abbreviations

a.a.

amino acid residue

20%-AA

20% acetic acid

AFM

atom force spectroscopy

CR

Congo Red

cryo-EM

cryoelectron microscopy

DSL

dynamic scattering light

H/D-exchange

hydrogen-deuterium exchange

IR

infrared spectroscopy

M/L

mass per length

MS

mass spectroscopy

NMR

nuclear magnetic resonance

PHF

paired helical filaments

RD

X-ray diffraction

Rg

radius of gyration

SANS

small-angle neutron diffraction

SAXS

small angle X-ray scattering

STEM

scanning transmission electron microscopy

TEM

transmission electron microscopy

ThS

Thioflavin S

ThT

Thioflavin T

Copyright information

© Pleiades Publishing, Ltd. 2012