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Jens Lagerstedt

Associate professor

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Structural and Functional Analysis of the ApolipoproteinA-I A164S Variant.

Author

  • Jonathan Dalla-Riva
  • Jens Lagerstedt
  • Jitka Petrlova

Summary, in English

Apolipoprotein A-I (apoA-I) is the main protein involved in the formation of high-density lipoprotein (HDL), it is the principal mediator of the reverse cholesterol transfer (RCT) pathway and provides cardio-protection. In addition to functional wild-type apoA-I, several variants have been shown to associate with hereditary amyloidosis. In this study we have performed biophysical and biochemical analyses of the structure and functional properties of the A164S variant of apoA-I (1:500 in the Danish general population), which is the first known mutation of apoA-I that leads to an increased risk of ischaemic heart disease (IHD), myocardial infarction and mortality without associated low HDL cholesterol levels. Despite the fact that epidemiologically IHD is associated with low plasma levels of HDL, the A164S mutation is linked to normal plasma levels of lipids, HDL and apoA-I, suggesting impaired functionality of this variant. Using biophysical techniques (e.g., circular dichroism spectroscopy and electron microscopy) to determine secondary structure, stability and pro-amyloidogenic property of the lipid free A164S apoA-I variant, our observations suggest similarity in structural properties between apoA-I WT and apoA-I A164S. However, the A164S apoA-I variant exhibits lower binding affinity to lipids but forms similar sized HDL particles to those produced by WT.

Department/s

  • Medical Protein Science
  • Dermatology and Venereology (Lund)
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2015

Language

English

Publication/Series

PLoS ONE

Volume

10

Issue

11

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 1932-6203