REVIEW: Structural Polymorphism and Possible Pathways of Amyloid Fibril Formation on the Example of Insulin Protein

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O. M. Selivanova and O. V. Galzitskaya^*

Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia; fax: (4967) 31-8435; E-mail: ogalzit@vega.protres.ru

^* To whom correspondence should be addressed.

Received March 20, 2012; Revision received May 15, 2012

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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.

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KEY WORDS: amyloid fibril, protofibril, oligomer, nucleus, insulin, injection amyloidosis

DOI: 10.1134/S0006297912110028

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