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Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I.

Petrlova, Jitka LU ; Bhattacherjee, Arnab; Boomsma, Wouter; Wallin, Stefan; Lagerstedt, Jens LU and Irbäck, Anders (2014) In Protein Science 23(11). p.1559-1571
Abstract
Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated disordered 1-93 fragment of this protein, in wild-type and mutated (G26R, S36A, K40L, W50R) forms. In atomic-level Monte Carlo simulations of the free monomer, validated by circular dichroism spectroscopy, we observe changes in the position-dependent β-strand probability induced by mutations. We find that these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy... (More)
Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated disordered 1-93 fragment of this protein, in wild-type and mutated (G26R, S36A, K40L, W50R) forms. In atomic-level Monte Carlo simulations of the free monomer, validated by circular dichroism spectroscopy, we observe changes in the position-dependent β-strand probability induced by mutations. We find that these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease-linked aggregation of apolipoprotein A-I. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Protein Science
volume
23
issue
11
pages
1559 - 1571
publisher
The Protein Society
external identifiers
  • pmid:25131953
  • wos:000344325900008
  • scopus:84928950006
ISSN
1469-896X
DOI
10.1002/pro.2534
language
English
LU publication?
yes
id
24ff9b24-5d22-4cb8-ad62-5b48635be025 (old id 4614447)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25131953?dopt=Abstract
date added to LUP
2014-09-07 16:27:10
date last changed
2017-10-08 03:14:45
@article{24ff9b24-5d22-4cb8-ad62-5b48635be025,
  abstract     = {Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated disordered 1-93 fragment of this protein, in wild-type and mutated (G26R, S36A, K40L, W50R) forms. In atomic-level Monte Carlo simulations of the free monomer, validated by circular dichroism spectroscopy, we observe changes in the position-dependent β-strand probability induced by mutations. We find that these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease-linked aggregation of apolipoprotein A-I.},
  author       = {Petrlova, Jitka and Bhattacherjee, Arnab and Boomsma, Wouter and Wallin, Stefan and Lagerstedt, Jens and Irbäck, Anders},
  issn         = {1469-896X},
  language     = {eng},
  number       = {11},
  pages        = {1559--1571},
  publisher    = {The Protein Society},
  series       = {Protein Science},
  title        = {Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I.},
  url          = {http://dx.doi.org/10.1002/pro.2534},
  volume       = {23},
  year         = {2014},
}