PXD021266-1

PXD021266 is an original dataset announced via ProteomeXchange.

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	2020-11-20
AnnouncementXML	Submission_2020-11-20_06:20:54.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

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.

10.1194/jlr.RA120000920;

submitter keyword: HDX-MS, Amyloidogenic ApoA-I variants

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/11/PXD021266

PRIDE project URI

• PRIDE
  1. PXD021266
     1. Label: PRIDE project
     2. Name: Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux