TY - JOUR
T1 - Phosphatidylethanolamine accelerates aggregation of the amyloidogenic N-terminal fragment of apoA-I
AU - Kurimitsu, Naoko
AU - Mizuguchi, Chiharu
AU - Fujita, Kaho
AU - Taguchi, Suzuno
AU - Ohgita, Takashi
AU - Nishitsuji, Kazuchika
AU - Shimanouchi, Toshinori
AU - Saito, Hiroyuki
N1 - Funding Information:
This work was partly supported by JSPS KAKENHI Grant Number JP17H03979 (H.S.) and the Hyogo Science and Technology Association (H.S.). The authors thank Dr. Michael C. Phillips (University of Pennsylvania) for valuable advice.
Publisher Copyright:
© 2020 Federation of European Biochemical Societies
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Membrane lipid composition is known to influence aggregation and fibril formation of many amyloidogenic proteins. Here, we found that phosphatidylethanolamine (PE) accelerates aggregation of the N-terminal 1‒83 fragment of an amyloidogenic G26R variant of apoA-I on lipid membranes. Circular dichroism and isothermal titration calorimetry measurements demonstrated that PE does not affect the α-helical structure and lipid binding property of apoA-I 1-83/G26R. Rather, fluorescence measurements indicated that PE induces more ordered lipid packing at the interfacial and acyl chain regions, providing more hydrophobic environments especially around the highly amyloidogenic regions in apoA-I on the membrane surface. These results suggest that PE promotes aggregation of the amyloidogenic N-terminal fragment of apoA-I on lipid membranes by inducing hydrophobic membrane environments.
AB - Membrane lipid composition is known to influence aggregation and fibril formation of many amyloidogenic proteins. Here, we found that phosphatidylethanolamine (PE) accelerates aggregation of the N-terminal 1‒83 fragment of an amyloidogenic G26R variant of apoA-I on lipid membranes. Circular dichroism and isothermal titration calorimetry measurements demonstrated that PE does not affect the α-helical structure and lipid binding property of apoA-I 1-83/G26R. Rather, fluorescence measurements indicated that PE induces more ordered lipid packing at the interfacial and acyl chain regions, providing more hydrophobic environments especially around the highly amyloidogenic regions in apoA-I on the membrane surface. These results suggest that PE promotes aggregation of the amyloidogenic N-terminal fragment of apoA-I on lipid membranes by inducing hydrophobic membrane environments.
KW - amyloid fibril
KW - apolipoprotein A-I
KW - lipid membrane
KW - phosphatidylethanolamine
KW - sphingomyelin
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U2 - 10.1002/1873-3468.13737
DO - 10.1002/1873-3468.13737
M3 - Article
C2 - 31968125
AN - SCOPUS:85078929306
VL - 594
SP - 1443
EP - 1452
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 9
ER -