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PXD021266

PXD021266 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux
DescriptionSpecific 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:51:16.015.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSimon Ekström
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-02 01:11:45ID requested
12020-11-20 06:20:54announced
22023-11-14 08:51:16announced2023-11-14: 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 affiliationDepartment 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 emailjens.lagerstedt@med.lu.se
lab head
Simon Ekström
contact affiliationBioMS - Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, BMC D1330, 221 84 Lund, Sweden
contact emailsimon.ekstrom@med.lu.se
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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