Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4614447
- author
- Petrlova, Jitka LU ; Bhattacherjee, Arnab ; Boomsma, Wouter ; Wallin, Stefan ; Lagerstedt, Jens LU and Irbäck, Anders
- organization
- publishing date
- 2014
- 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
- pmid:25131953
- 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
- 2016-04-01 10:39:16
- date last changed
- 2022-01-26 01:13:21
@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}},
doi = {{10.1002/pro.2534}},
volume = {{23}},
year = {{2014}},
}