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

Petrlova, Jitka LU ; Dalla-Riva, Jonathan LU ; Mörgelin, Matthias LU ; Lindahl, Maria LU ; Krupinska, Ewa LU ; Stenkula, Karin LU ; Voss, John LU and Lagerstedt, Jens LU (2014) In PLoS ONE 9(4).
Abstract
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... (More)
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. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
9
issue
4
publisher
Public Library of Science
external identifiers
  • pmid:24755625
  • wos:000335240300142
  • scopus:84899688966
ISSN
1932-6203
DOI
10.1371/journal.pone.0096150
language
English
LU publication?
yes
id
1c9a3840-9618-43c5-acee-5cc4e96fac3b (old id 4429598)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24755625?dopt=Abstract
date added to LUP
2014-05-08 08:31:46
date last changed
2017-11-12 03:44:06
@article{1c9a3840-9618-43c5-acee-5cc4e96fac3b,
  abstract     = {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.},
  articleno    = {e96150},
  author       = {Petrlova, Jitka and Dalla-Riva, Jonathan and Mörgelin, Matthias and Lindahl, Maria and Krupinska, Ewa and Stenkula, Karin and Voss, John and Lagerstedt, Jens},
  issn         = {1932-6203},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Secondary Structure Changes in ApoA-I Milano (R173C) Are Not Accompanied by a Decrease in Protein Stability or Solubility.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0096150},
  volume       = {9},
  year         = {2014},
}