Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes
(2024) In Protein Science 33(5).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2024-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloidogenic variants, apolipoprotein A-I, high-density lipoprotein, reconstituted HDL
- in
- Protein Science
- volume
- 33
- issue
- 5
- article number
- e4987
- pages
- 16 pages
- publisher
- The Protein Society
- external identifiers
-
- scopus:85190272905
- pmid:38607188
- ISSN
- 0961-8368
- DOI
- 10.1002/pro.4987
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2024 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
- id
- faabb4b9-6dfa-432e-9e94-10c31201f823
- date added to LUP
- 2024-05-14 20:14:06
- date last changed
- 2024-08-23 13:23:38
@article{faabb4b9-6dfa-432e-9e94-10c31201f823, abstract = {{<p>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.</p>}}, author = {{Correa, Yubexi and Ravel, Mathilde and Imbert, Marie and Waldie, Sarah and Clifton, Luke and Terry, Ann and Roosen-Runge, Felix and Lagerstedt, Jens O. and Moir, Michael and Darwish, Tamim and Cárdenas, Marité and Del Giudice, Rita}}, issn = {{0961-8368}}, keywords = {{amyloidogenic variants; apolipoprotein A-I; high-density lipoprotein; reconstituted HDL}}, language = {{eng}}, number = {{5}}, publisher = {{The Protein Society}}, series = {{Protein Science}}, title = {{Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes}}, url = {{http://dx.doi.org/10.1002/pro.4987}}, doi = {{10.1002/pro.4987}}, volume = {{33}}, year = {{2024}}, }