PXD042501-2

PXD042501 is an original dataset announced via ProteomeXchange.

Title	Cross-linked amyloidogenic proteins as potential aggregation inhibitors
Description	Amyloidogenic proteins, characterized by their ability to form fibrillar aggregates with β sheet structure play an important role in several degenerative diseases, including Parkinson’s disease. Numerous amyloidogenic proteins, such as α synuclein, are intrinsically disordered (or contain ID regions, hence they also present as highly dynamic conformational ensembles in these regions. Aggregation is an inherent property of the polypeptide chains and under non physiological, appropriate conditions most of the proteins can aggregate and form polymers of various structures. Since amyloid fib ril s and oligomers are associated with a great variety of human diseases, inhibition of protein aggregation has great importance and it can be addressed by using small molecules, peptides or proteins. Our research aim was to study the potential application of modified forms of different amyloidogenic proteins as inhibitor molecules by introducing structural constraints in them. Under various conditions, different amyloidogenic proteins’ (α-synuclein and β2-microglobulin) monomer molecules have been cross linked intramolecularly and the heterogeneous mixtures has been fractionated by HPLC. The inhibitory potential of the isolated and effective molecules has been experimentally investigated by various methods ThT assay, TEM, CD spectroscopy). Furthermore, the locations of the crosslinks in the molecules were determined by mass spectrometry, and their structures are modeled in silico. Our results revealed that conformational constrains applied by cross linking on amyloidogenic proteins block their amyloid formation. Moreover, these molecules exhibited inhibitory effect on the aggregation of the unmodified proteins, as well.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:11:30.610.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gabriella Gellen
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	SELECT SERIES Cyclic IMS

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-25 09:46:49	ID requested
1	2023-10-24 13:33:11	announced
⏵ 2	2023-11-14 09:11:38	announced	2023-11-14: Updated project metadata.

Murvai N, Gellen G, Micsonai A, Schlosser G, Kardos J, -Synuclein as Inhibitor of Amyloid Formation. Int J Mol Sci, 24(17):(2023) [pubmed]

submitter keyword: LC-MS/MS, α-synuclein, cross-linking MS

Dr. Gitta Schlosser
contact affiliation	MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Eotvos Lorand University, Hungary
contact email	gitta.schlosser@ttk.elte.hu
lab head
Gabriella Gellen
contact affiliation	MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Department of Analytical Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, 1117 Budapest, Hungary
contact email	gabgellen@staff.elte.hu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042501
     1. Label: PRIDE project
     2. Name: Cross-linked amyloidogenic proteins as potential aggregation inhibitors