PXD021266 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux |
Description | Specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis. Carriers do not exhibit increased cardiovascular disease risk despite reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of L75P and L174S patients presents a higher relative abundance of the 8.4 nm vs 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 compared to 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:51:16.015.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Simon Ekström |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-09-02 01:11:45 | ID requested | |
1 | 2020-11-20 06:20:54 | announced | |
⏵ 2 | 2023-11-14 08:51:16 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: HDX-MS, Amyloidogenic ApoA-I variants |
Contact List
Jens O. Lagerstedt |
contact affiliation | Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden Lund Institute of Advanced Neutron and X-ray Science (LINXS), SE-221 84 Lund, Sweden |
contact email | jens.lagerstedt@med.lu.se |
lab head | |
Simon Ekström |
contact affiliation | BioMS - Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, BMC D1330, 221 84 Lund, Sweden |
contact email | simon.ekstrom@med.lu.se |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021266
- Label: PRIDE project
- Name: Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux