Early stages of insulin fibrillogenesis examined with ion mobility mass spectrometry and molecular modelling

Research output: Contribution to journalArticle

  • External authors:
  • H Cole
  • M Porrini
  • R Morris
  • T Smith
  • J Kalapothakis
  • S Weidt
  • C L Mackay
  • C E MacPhee

Abstract

A prevalent type of protein misfolding causes the formation of beta-sheet-rich structures known as amyloid fibrils. Research into the mechanisms of fibril formation has implications for both disease prevention and nanoscale templating technologies. This investigation into the aggregation of insulin utilises ion mobility mass spectrometry coupled with molecular modelling to identify and characterise oligomers formed during the 'lag' phase that precedes fibril growth. High resolution mass spectrometry and collision induced dissociation is used to unequivocally assign species as m/z coincident multimers or confomers, providing a robust analytical approach that supports the use of molecular dynamics to atomistically resolve the observed oligomers. We show that insulin oligomerises to form species In where 2

Bibliographical metadata

Original languageEnglish
Pages (from-to)7000-11
Number of pages6988
JournalAnalyst
Volume140
Issue number20
DOIs
StatePublished - 2015