Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural analysis of human Clusterin/ApoJ, part 2

ABSTRACT: 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 genetic risk factor for late-onset Alzheimer's disease. To better understand its 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).

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Andreas Bracher

LAB HEAD: F Ulrich Hartl

PROVIDER: PXD056940 | Pride | 2025-07-22

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	2WT-Clu_rep1_20240215_Sample02.raw	Raw
	P10909.fasta	Fasta
	Sample_Processing_Protocol_limited_proteolysis.docx	Other
	TL4_Clu-R227Q.fasta	Fasta
	TL4_rep1_20240415_Sample01.raw	Raw

Items per page:

1 - 5 of 30

Similar Datasets

Structural analysis of human Clusterin/ApoJ, part 1

Project 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).

2025-07-22 | PXD057022 | Pride

siRNA profiling of human synovial fibroblasts depleted for clusterin

Project description:Analysis of synoviocytes cell form patients suffering of Rheumatoid arthritis and depleted for clusterin by siRNA knockdown. Note: this experiment was reloaded into ArrayExpress on 2nd December 2009 because the incorrect array design had originally been selected. The identifiers in the datafile were also fixed to match the array design.

2009-12-04 | E-TABM-653 | biostudies-arrayexpress

Isotopic N,N-dimethyl leucine tags for absolute quantification of clusterin and apolipoprotein E in Alzheimer's disease

Project description:Alzheimer’s disease (AD) is the most common form of dementia and one of the leading causes of death in the United States. In past decades, extensive efforts have been devoted to improving our understanding of AD pathogenesis and accelerating biomarker discovery for early diagnosis and clinical treatment of AD. Herein, this study aims to quantify clusterin (CLU) and apolipoprotein E (APOE) in blood samples from AD patients and evaluate these two proteins as potential biomarkers in AD diagnosis. In-house synthesized 5-plex isotopic N,N-dimethyl leucine (iDiLeu) tags were used to label target peptide standards at different concentrations to construct standard curves. Our study reveals that the levels of CLU and APOE exhibit clear disparities in male vs. female AD groups but not in male vs. female non-AD groups, while the levels of serum CLU and APOE do not show statistical differences in the AD groups and non-AD groups. Principal component analysis (PCA) with CLU and APOE showed some separation between the AD and non-AD participants. Significance: Dissecting CLU and APOE heterogeneity in AD pathogenesis may therefore facilitate delineating the pathological relevance for specific pathways between different genders, leading to personalized medicine in the future. Collectively, this study introduces a cost-effective absolute quantitative proteomics strategy for target protein quantitation and lays the foundation for future investigation of CLU and APOE as potential biomarkers for AD.

2022-10-05 | PXD030724 | Pride

Beyond a Linear Structure: The Tubular Organization of the Tripartite Attachment Complex and the Functional Role of TAC53

Project description:Trypanosoma IP experiment: Beyond a Linear Structure: The Tubular Organization of the Tripartite Attachment Complex and the Functional Role of TAC53

2025-08-04 | PXD061646 | Pride

Murine hippocampal proteome - Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus

Project description:The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve interconnecting transcription-translation feedback loops. The hippocampus plays an important role in spatial memory and the conversion of short-term to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus, and have highlighted the importance of circadian regulation in memory formation. In this study we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry.

2017-04-11 | PXD005668 | Pride

Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems

Project description:Comparison of the methylation profile of mouse embryonic fibroblasts (MEFs) before and during adaptation to cell culture conditions. Matched expression data is deposited under accession: E-MTAB-3172

2014-12-17 | E-MTAB-3176 | biostudies-arrayexpress

Cholesterol lowering depletes smooth muscle cell-derived fibromyocytes and chondromyocytes from atherosclerotic lesions

Project description:Study of the effect of low-density lipoprotein (LDL)-lowering therapies on the heterogeneous population of proliferating smooth muscle cells (SMCs) derived from atherosclerotic plaques in an atherosclerotic mouse model by inducing hypercholesterolemia followed by high or low fat diet.

2023-12-08 | E-MTAB-12019 | biostudies-arrayexpress

Chromatin accessibility (ATAC-seq) of human acute leukemias and healthy donors

Project description:ATAC-seq of 79 primary samples obtained from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Moreover, ATAC-seq of CD34+ HSPCs from 3 healthy donors are included. ATAC-seq was performed as described (Buenrostro et al., 2013) with a modification in the lysis buffer to reduce mitochondrial DNA contamination. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011050 (dataset).

2023-08-31 | E-MTAB-13118 | biostudies-arrayexpress

Spatial rearrangement of the Streptomyces venezuelae linear chromosome during sporogenic development

Project description:Hi-C analysis of the chromosome organization during sporulation in Streptomyces venezuelae. The experiment includes the effect of ParA, ParB, SMC, and HupS proteins on the chromosome structure.

2020-12-09 | E-MTAB-9810 | biostudies-arrayexpress

miRNAs in RPE cells treated by clusterin

Project description:Clusterin has been indicated to protect human retinal pigment epithelial (RPE) cells from oxidative stress-induced apoptosis. This study was conducted to identify aberrantly expressed microRNAs (miRNAs) downstream clusterin in RPE cells.

2016-09-21 | GSE87115 | GEO