Biochemistry (Moscow)

, Volume 77, Issue 11, pp 1237–1247

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



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 fibril protofibril oligomer nucleus insulin injection amyloidosis 



amino acid residue


20% acetic acid


atom force spectroscopy


Congo Red


cryoelectron microscopy


dynamic scattering light


hydrogen-deuterium exchange


infrared spectroscopy


mass per length


mass spectroscopy


nuclear magnetic resonance


paired helical filaments


X-ray diffraction


radius of gyration


small-angle neutron diffraction


small angle X-ray scattering


scanning transmission electron microscopy


transmission electron microscopy


Thioflavin S


Thioflavin T


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Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  1. 1.Institute of Protein ResearchRussian Academy of SciencesPushchino, Moscow RegionRussia

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