PXD020858 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis |
Description | Amyloid fibrils are polymeric structures originating from aggregation of misfolded proteins. In vivo, proteolysis may modulate amyloidogenesis and fibril stability. In light chain (AL) amyloidosis, fragmented light chains (LCs) are abundant components of amyloid deposits; however, site and timing of proteolysis are debated. Identification of the N- and C-termini of LC fragments is instrumental to understanding involved processes and enzymes. We investigated the N- and C-terminome of the LC proteoforms in fibrils extracted from the hearts of two AL cardiomyopathy patients, using a proteomic approach based on derivatization of N- and C-terminal residues, followed by mapping of fragmentation sites on the structures of native and fibrillar relevant LCs. We provide the first high-specificity map of proteolytic cleavages in natural AL amyloid. Proteolysis occurs both on the LCs’ variable and constant domains, generating a complex fragmentation pattern. The structural analysis indicates extensive remodeling, by multiple proteases, largely taking place on poorly folded regions of the fibril surfaces. This study adds novel important knowledge on amyloid LCs processing: although our data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, they show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils. |
HostingRepository | PRIDE |
AnnounceDate | 2020-10-15 |
AnnouncementXML | Submission_2020-10-15_05:50:53.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Giulia Mazzini |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | amidated residue; dimethylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-08-11 17:03:38 | ID requested | |
⏵ 1 | 2020-10-15 05:50:54 | announced | |
Publication List
Lavatelli F, Mazzini G, Ricagno S, Iavarone F, Rognoni P, Milani P, Nuvolone M, Swuec P, Caminito S, Tasaki M, Chaves-Sanjuan A, Urbani A, Merlini G, Palladini G, Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis. J Biol Chem, 295(49):16572-16584(2020) [pubmed] |
Keyword List
submitter keyword: Proteomics, Amyloid fibrils, Mass Spectrometry, Proteolysis, Cardiomyopathy |
Contact List
Giovanni Palladini |
contact affiliation | Amyloidosis Treatment and Research Center, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Italy |
contact email | g.palladini@smatteo.pv.it |
lab head | |
Giulia Mazzini |
contact affiliation | Fondazione IRCCS Policlinico San Matteo |
contact email | g.mazzini@smatteo.pv.it |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020858
- Label: PRIDE project
- Name: Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis