Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I
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Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I. / Petrlova, Jitka; Bhattacherjee, Arnab; Boomsma, Wouter Krogh; Wallin, Stefan; Lagerstedt, Jens O.; Irbäck, Anders.
In: Protein Science, Vol. 23, No. 11, 2014, p. 1559-1571.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I
AU - Petrlova, Jitka
AU - Bhattacherjee, Arnab
AU - Boomsma, Wouter Krogh
AU - Wallin, Stefan
AU - Lagerstedt, Jens O.
AU - Irbäck, Anders
N1 - © 2014 The Protein Society.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1002/pro.2534
DO - 10.1002/pro.2534
M3 - Journal article
C2 - 25131953
VL - 23
SP - 1559
EP - 1571
JO - Protein Science
JF - Protein Science
SN - 0961-8368
IS - 11
ER -
ID: 123508160