Structural and Functional Analysis of the ApolipoproteinA-I A164S Variant.
(2015) In PLoS ONE 10(11).- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8234548
- author
- Dalla-Riva, Jonathan LU ; Lagerstedt, Jens LU and Petrlova, Jitka LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 10
- issue
- 11
- article number
- e0143915
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:26605794
- wos:000365865300123
- scopus:84955594337
- pmid:26605794
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0143915
- language
- English
- LU publication?
- yes
- id
- 1f7fd750-207f-43ba-9eeb-07c4d165d8da (old id 8234548)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26605794?dopt=Abstract
- date added to LUP
- 2016-04-01 15:02:44
- date last changed
- 2022-04-06 21:57:33
@article{1f7fd750-207f-43ba-9eeb-07c4d165d8da, abstract = {{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.}}, author = {{Dalla-Riva, Jonathan and Lagerstedt, Jens and Petrlova, Jitka}}, issn = {{1932-6203}}, language = {{eng}}, number = {{11}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS ONE}}, title = {{Structural and Functional Analysis of the ApolipoproteinA-I A164S Variant.}}, url = {{http://dx.doi.org/10.1371/journal.pone.0143915}}, doi = {{10.1371/journal.pone.0143915}}, volume = {{10}}, year = {{2015}}, }