Structural Insight of Amyloidogenic Intermediates of Human Insulin

ACS Omega
Sandip DoluiNakul C Maiti

Abstract

Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibrilization and determined the structural content present in oligomer and protofibrils that are formed as intermediates in the fibril formation pathway. Insulin oligomer, as obtained upon incubation of zinc-free insulin at 60 °C, was mostly spherical in shape, with a diameter of 3-5 nm. Longer incubation produced "necklace"-like beaded protofibrillar assembly species. These intermediates eventually transformed into 5-8 nm thick fibers with smooth surface texture. A broad amide I band in the Raman spectrum of insulin monomer appeared at 1659 cm-1, with a shoulder band at 1676 cm-1. This signature suggested the presence of major helical and extended secondary structure of the protein backbone. In the oligomeric state, the protein maintained its helical imprint (∼50%) and no substantial increment of the compact cross-β-sheet structure was observed. A nonamide helix signature band at 940 cm-1 was present in the oligomeric state, and it was weakened in the fibrillar structure. The 1-anilino-8-naphthalene-sulfonate binding study strongly suggested that a collapse in the tertiary structure, not the major secondary structural realignment, was t...Continue Reading

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Citations

Nov 8, 2020·International Journal of Biological Macromolecules·Aruna K MoraSukhendu Nath
Mar 2, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Sérgio R S VelosoPaula M T Ferreira
Apr 17, 2021·International Journal of Biological Macromolecules·Mohammad Irshad RezaJiaur R Gayen
Jul 3, 2021·International Journal of Molecular Sciences·Marco DiociaiutiGiovanna D'Arcangelo
Aug 10, 2021·International Journal of Biological Macromolecules·Sudeshna Ghosh, Sandeep Verma
Jan 21, 2020·The Journal of Physical Chemistry. B·Bhisma N RathaAnirban Bhunia

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Methods Mentioned

BETA
NMR
X-ray
atomic force microscopy
circular dichroism
fluorescence assay
Fluorescence
AFM
electrophoresis
Fluorescence Spectroscopy

Software Mentioned

A1
AI
GRAMS
Pico view

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