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Secondary Structure Changes in ApoA-I Milano (R173C) Are Not Accompanied by a Decrease in Protein Stability or Solubility.

Author:
  • Jitka Petrlova
  • Jonathan Dalla-Riva
  • Matthias Mörgelin
  • Maria Lindahl
  • Ewa Krupinska
  • Karin Stenkula
  • John Voss
  • Jens Lagerstedt
Publishing year: 2014
Language: English
Publication/Series: PLoS ONE
Volume: 9
Issue: 4
Document type: Journal article
Publisher: Public Library of Science

Abstract english

Apolipoprotein A-I (apoA-I) is the main protein of high-density lipoprotein (HDL) and a principal mediator of the reverse cholesterol transfer pathway. Variants of apoA-I have been shown to be associated with hereditary amyloidosis. We previously characterized the G26R and L178H variants that both possess decreased stability and increased fibril formation propensity. Here we investigate the Milano variant of apoAI (R173C; apoAI-M), which despite association with low plasma levels of HDL leads to low prevalence of cardiovascular disease in carriers of this mutation. The R173C substitution is located to a region (residues 170 to 178) that contains several fibrillogenic apoA-I variants, including the L178H variant, and therefore we investigated a potential fibrillogenic property of the apoAI-M protein. Despite the fact that apoAI-M shared several features with the L178H variant regarding increased helical content and low degree of ThT binding during prolonged incubation in physiological buffer, our electron microscopy analysis revealed no formation of fibrils. These results suggest that mutations inducing secondary structural changes may be beneficial in cases where fibril formation does not occur.

Keywords

  • Infectious Medicine
  • Cell and Molecular Biology

Other

Published
  • Medical Protein Science
  • ISSN: 1932-6203
Maria Lindahl
E-mail: maria.lindahl [at] med.lu.se

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