Search: onr:"swepub:oai:lup.lub.lu.se:424c7415-4ef1-4a65-9cf7-0e6d201d46bd" >
Structure dynamics ...
Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux
-
- Nilsson, Oktawia (author)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
-
- Lindvall, Mikaela (author)
- Lund University
-
- Obici, Laura (author)
- Policlinico San Matteo Pavia Fondazione
-
show more...
-
- Ekström, Simon (author)
- Lund University,Lunds universitet,BioMS,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
- Lagerstedt, Jens O. (author)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,LINXS - Institute of advanced Neutron and X-ray Science,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Medical Protein Science,Lund University Research Groups,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
-
- Del Giudice, Rita (author)
- Lund University,Lunds universitet
-
show less...
-
(creator_code:org_t)
- 2021
- 2021
- English.
-
In: Journal of Lipid Research. - 0022-2275. ; 62
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Apolipoprotein A-I (ApoA-I) of high density lipoproteins (HDLs) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in ApoA-I of HDLs are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL cholesterol. To explain this paradox, we show that the HDL particle profiles of patients carrying either L75P or L174S ApoA-I amyloidogenic variants show a higher relative abundance of the 8.4-nm versus 9.6-nm particles and that serum from patients, as well as reconstituted 8.4- and 9.6-nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogendeuterium exchange revealed that the variants in 8.4-nm rHDL have altered secondary structure composition and display a more flexible binding to lipids than their native counterpart. The reduced HDL cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles, and better cholesterol efflux due to altered, region-specific protein structure dynamics.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Amyloidosis
- Apolipoprotein A-I
- Apolipoproteins
- Cardiovascular disease
- Cholesterol efflux
- High density lipoprotein/HDL
- Hydrogen-deuterium exchange/HDX
- Protein structure
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database