Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes

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Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes

Correa, Yubexi (author): Malmö universitet,Biofilms Research Center for Biointerfaces,Institutionen för biomedicinsk vetenskap (BMV)

Ravel, Mathilde (author): Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces

Imbert, Marie (author): Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces

Waldie, Sarah (author): Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces

Clifton, Luke (author): Harwell Sci & Innovat Campus, Sci & Technol Facil Council, Rutherford Appleton Lab, ISIS Pulsed Neutron & Muon Source, Didcot, England.

Terry, Ann (author): Lund Univ, MAX Lab 4, CoSAXS Beamline, Lund, Sweden.

Roosen-Runge, Felix (author): Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces

Lagerstedt, Jens O. (author): Lund Univ, Diabet Ctr, Dept Clin Sci Malmö, Islet Cell Exocytosis, Malmö, Sweden.;Novo Nordisk, Rare Endocrine Disorders, Res & Early Dev, Copenhagen, Denmark.

Moir, Michael (author): Australian Nucl Sci & Technol Org ANSTO, Natl Deuterat Facil, Lucas Heights, NSW, Australia.

Darwish, Tamim (author): Australian Nucl Sci & Technol Org ANSTO, Natl Deuterat Facil, Lucas Heights, NSW, Australia.;Univ Canberra, Fac Sci & Technol, Canberra, ACT, Australia.

Cárdenas, Marité (author): Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Basque Fdn Sci, Ikerbasque, Bilbao, Spain.;Univ Basque Country, Biofis Inst, Leioa, Spain.

Del Giudice, Rita (author): Malmö universitet,Biofilms Research Center for Biointerfaces,Institutionen för biomedicinsk vetenskap (BMV)

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John Wiley & Sons, 2024
2024
English.
In: Protein Science. - : John Wiley & Sons. - 0961-8368 .- 1469-896X. ; 33:5

Related links:: https://doi.org/10.1...; show more...; https://mau.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoA-I), is essential to this process, and changes in its sequence significantly alter HDL structure and functions. ApoA-I amyloidogenic variants, associated with a particular hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA-I proteins with functional/structural features similar to those of amyloidogenic variants hold potential as a promising therapeutic approach. Here we explored the effect of protein cargo and lipid composition on the function of rHDL containing one of the ApoA-I amyloidogenic variants G26R or L174S by Fourier transformed infrared spectroscopy and neutron reflectometry. Moreover, small-angle x-ray scattering uncovered the structural and functional differences between rHDL particles, which could help to comprehend higher cholesterol efflux activity and apparent lower phospholipid (PL) affinity. Our findings indicate distinct trends in lipid exchange (removal vs. deposition) capacities of various rHDL particles, with the rHDL containing the ApoA-I amyloidogenic variants showing a markedly lower ability to remove lipids from artificial membranes compared to the rHDL containing the native protein. This effect strongly depends on the level of PL unsaturation and on the particles' ultrastructure. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid-protein interactions and their behavior.

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

amyloidogenic variants
apolipoprotein A-I
high-density lipoprotein
reconstituted HDL

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ref (subject category)
art (subject category)

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By the author/editor: Correa, Yubexi; Ravel, Mathilde; Imbert, Marie; Waldie, Sarah; Clifton, Luke; Terry, Ann; show more...; Roosen-Runge, Fe ...; Lagerstedt, Jens ...; Moir, Michael; Darwish, Tamim; Cárdenas, Marité; Del Giudice, Rit ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Articles in the publication: Protein Science

By the university: Malmö University

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