PXD057022

PXD057022 is an original dataset announced via ProteomeXchange.

Title	Structural analysis of human Clusterin/ApoJ, part 1
Description	The conserved human secreted glycoprotein Clusterin (aka Apolipoprotein-J, ApoJ) is an abundant component of body fluids such as blood plasma and cerebrospinal fluid. Clusterin is thought to function as an extracellular molecular chaperone stabilizing misfolded proteins in solution. In addition, clusterin forms lipoprotein complexes and fractions with HDL particles in plasma. Variants of the clusterin gene constitute the third most important risk factor for late-onset Alzheimer's disease. To better understand it structure and functions, the crystal structure of a mutant form of Clusterin was determined. In order to validate the structural data, hydrogen-deuterium exchange kinetics followed by pepsin proteolysis and mass spectrometry analysis of recombinant mutant and wildtype protein were performed (Part 1 of the deposited data). Based on the structure, rational mutants were designed and subjected to functional tests such as chaperone activity, cellular uptake and receptor binding and lipoprotein complex formation. In order to probe the conformation of Clusterin in the lipoprotein complex, free and lipid-bound protein were subjected to limited proteolysis with chymotrypsin and the resultant fragments analyzed by LC/MS proteomics (Part 2 of the deposited data).
HostingRepository	PRIDE
AnnounceDate	2025-07-22
AnnouncementXML	Submission_2025-07-22_08:02:57.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Bracher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-21 10:21:54	ID requested
⏵ 1	2025-07-22 08:02:57	announced

10.1038/S41594-025-01631-4;

submitter keyword: Human, cerebrospinal fluid, hydrogen-deuterium exchange, limited proteolysis, apolipoprotein, plasma, extracellular chaperone, rational mutagenesis

F. Ulrich Hartl
contact affiliation	Max-Planck-Institute of Biochemistry Department of Cellular Biochemistry Am Klopferspitz 18 82152 Martinsried Germany
contact email	uhartl@biochem.mpg.de
lab head
Andreas Bracher
contact affiliation	Max-Planck-Institute of Biochemistry Dept. of Cellular Biochemistry Am Klopferspitz 18 82152 Martinsried
contact email	bracher@biochem.mpg.de
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/2025/07/PXD057022

PRIDE project URI

• PRIDE
  1. PXD057022
     1. Label: PRIDE project
     2. Name: Structural analysis of human Clusterin/ApoJ, part 1