Structural analysis of human Clusterin/ApoJ, part 2 Version 1
External LinkThe 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).
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Created: 26th Nov 2025 at 13:58
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Version 1 (earliest) Created 26th Nov 2025 at 13:58 by Aditi Methi
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Projects: SyNergy: Published Datasets, SyNergy: Unpublished Datasets
Institutions: LMU Klinikum
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Neurological diseases are on the rise – and as societies age, they affect an ever-increasing number of people, not only in Europe, but worldwide.
The Munich Cluster for Systems Neurology (SyNergy) investigates how complex neurological diseases such as Alzheimer's disease, stroke, and multiple sclerosis develop. Even though these diseases differ in their clinical manifestations, overlapping mechanisms are involved in their development. For example, the immune system gets activated in dementia, ...
Projects: SyNergy: Published Datasets, SyNergy: Unpublished Datasets
Web page: https://www.synergy-munich.de
This project serves as a centralized repository for omics datasets published by research groups within the SyNergy Cluster. It encompasses investigations such as proteomics and transcriptomics, which are further divided into individual studies led by SyNergy members. Each study is linked to relevant publications, assays and data files (with links to external repositories).
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Clusterin (apolipoprotein J), a conserved glycoprotein abundant in blood and cerebrospinal fluid, functions as a molecular chaperone and apolipoprotein. Dysregulation of clusterin is linked to late-onset Alzheimer disease. Despite its prominent role in extracellular proteostasis, the mechanism of clusterin function remained unclear. Here, we present crystal structures of human clusterin, revealing a discontinuous three-domain architecture. Structure-based mutational analysis demonstrated that two ...
Submitter: Aditi Methi
Assay type: Proteomics
Technology type: Mass Spectrometry
Investigation: Proteomics (Published)
