دورية أكاديمية
Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux
| العنوان: | Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux |
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| المؤلفون: | Nilsson, Oktawia, Lindvall, Mikaela, Obici, Laura, Ekstrom, Simon, Lagerstedt, Jens O., Del Giudice, Rita |
| بيانات النشر: | Malmö universitet, Institutionen för biomedicinsk vetenskap (BMV) Lund Univ, Dept Expt Med Sci, Lund, Sweden. Fdn IRCCS Policlin San Matteo, Amyloidosis Res & Treatment Ctr, Pavia, Italy. Lund Univ, BioMS Swedish Natl Infrastruct Biol Mass Spectrom, Lund, Sweden. Lund Univ, Dept Expt Med Sci, Lund, Sweden.;Lund Inst Adv Neutron & Xray Sci LINXS, Lund, Sweden. Lund Univ, Dept Expt Med Sci, Lund, Sweden |
| سنة النشر: | 2021 |
| المجموعة: | Malmö University Electronic Publishing (MUEP) |
| مصطلحات موضوعية: | apolipoproteins, apolipoprotein A-I, amyloidosis, high density lipoprotein/HDL, cholesterol efflux, cardiovascular disease, protein structure, hydrogen-deuterium exchange/HDX, Cell and Molecular Biology, Cell- och molekylärbiologi |
| الوصف: | 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 hydrogen-deuterium 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Journal of Lipid Research, 0022-2275, 2021, 62; orcid:0000-0002-9927-9413; http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-44009Test; PMID 33410751; ISI:000651390200001; Scopus 2-s2.0-85100681456 |
| DOI: | 10.1194/jlr.RA120000920 |
| الإتاحة: | https://doi.org/10.1194/jlr.RA120000920Test http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-44009Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.980A1B68 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1194/jlr.RA120000920 |
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