Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I
(2014) In Protein Science 23(11). p.71-1559- 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.
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- author
- Petrlova, Jitka
LU
; Bhattacherjee, Arnab
LU
; Boomsma, Wouter
LU
; Wallin, Stefan
LU
; Lagerstedt, Jens O
LU
and Irbäck, Anders
LU
- organization
- publishing date
- 2014-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amyloid, Apolipoprotein A-I, Circular Dichroism, Intrinsically Disordered Proteins, Molecular Dynamics Simulation, Protein Structure, Secondary
- in
- Protein Science
- volume
- 23
- issue
- 11
- pages
- 13 pages
- publisher
- The Protein Society
- external identifiers
-
- scopus:84928950006
- wos:000344325900008
- pmid:25131953
- ISSN
- 1469-896X
- DOI
- 10.1002/pro.2534
- language
- English
- LU publication?
- yes
- id
- 4038a8fb-13d3-4b22-b70b-743cb6e1a95f
- date added to LUP
- 2016-08-16 18:03:47
- date last changed
- 2024-09-06 20:20:01
@article{4038a8fb-13d3-4b22-b70b-743cb6e1a95f, abstract = {{<p>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.</p>}}, author = {{Petrlova, Jitka and Bhattacherjee, Arnab and Boomsma, Wouter and Wallin, Stefan and Lagerstedt, Jens O and Irbäck, Anders}}, issn = {{1469-896X}}, keywords = {{Amyloid; Apolipoprotein A-I; Circular Dichroism; Intrinsically Disordered Proteins; Molecular Dynamics Simulation; Protein Structure, Secondary}}, language = {{eng}}, number = {{11}}, pages = {{71--1559}}, 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}}, }