Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HDX-MS of alpha-synuclein oligomers

ABSTRACT: Here we have used HDX-MS to investigate the change in structure/dynamics in synuclein oligomers formed under different conditions.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Antonio Calabrese

LAB HEAD: Sheena Radford

PROVIDER: PXD038573 | Pride | 2024-05-24

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	HDXSalvaRepeat_New.DnX	Other
	bsejb_220629_01.raw.zip	Raw
	bsejb_220629_03.raw.zip	Raw
	bsejb_220629_05.raw.zip	Raw
	bsejb_220629_07.raw.zip	Raw

Items per page:

1 - 5 of 49

Publications

A Targetable N-Terminal Motif Orchestrates α-Synuclein Oligomer-to-Fibril Conversion.

Santos Jaime J Cuellar Jorge J Pallarès Irantzu I Byrd Emily J EJ Lends Alons A Moro Fernando F Abdul-Shukkoor Muhammed Bilal MB Pujols Jordi J Velasco-Carneros Lorea L Sobott Frank F Otzen Daniel E DE Calabrese Antonio N AN Muga Arturo A Pedersen Jan Skov JS Loquet Antoine A Valpuesta Jose María JM Radford Sheena E SE Ventura Salvador S

Journal of the American Chemical Society 20240429 18

Oligomeric species populated during α-synuclein aggregation are considered key drivers of neurodegeneration in Parkinson's disease. However, the development of oligomer-targeting therapeutics is constrained by our limited knowledge of their structure and the molecular determinants driving their conversion to fibrils. Phenol-soluble modulin α3 (PSMα3) is a nanomolar peptide binder of α-synuclein oligomers that inhibits aggregation by blocking oligomer-to-fibril conversion. Here, we investigate th ...[more]

PMID: 38683963

Similar Datasets

HDX-MS data of BAM and SurA binding

Project description:We present HDX-MS data of the BAM:SurA complex to define the interaction sites for SurA on BAM and vice versa.

2022-07-12 | PXD030268 | Pride

Binding of a bovine ultralong CDRH3 to the SARS-CoV RBD

Project description:Here, we have used a SARS-naïve, bovine ultralong CDRH3 library to isolate a bovine paratope that engages the SARS-CoV and SARS-CoV-2 receptor-binding domain (RBD). This scFv (B9-scFv) neutralises viruses pseudo-typed with SARS-CoV Spike protein. Using differential hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis, we demonstrate that this CDRH3 recognises a conserved, cryptic epitope.

2023-03-11 | PXD032965 | Pride

Inter-domain dynamics in the chaperone SurA and multi-site binding to its unfolded outer membrane protein clients revealed by HDX-MS

Project description:We present HDX-MS data of apo-SurA, SurA in complex with OmpX, OmpF and a peptide with sequence WEYIPNV to define (1) interdomain dynamics in the periplasmic chaperone SurA, and (2) the binding site of OmpX, OmpF and WEYIPNV on SurA.

2020-05-22 | PXD017010 | Pride

Effects of ATP binding on the conformational flexibility of proNGF

Project description:Nerve growth factor (NGF) is involved in the maintenance and growth of specific neuronal populations whereas its precursor, proNGF, shows opposite properties, like being involved in apoptosis. NGF/proNGF imbalance is linked to neurodegeneration. Here, we show that ATP binds to proNGF inducing an overall proNGF shape change, throughout a local conformational rearrangement of the flexible pro-peptide domain. This suggests a functional role for ATP in the modulation of proNGF/NGF physiological homeostasis.

2023-11-16 | PXD035625 | Pride

LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry.

Project description:Insertion of lipopolysaccharide (LPS) into the outer membrane (OM) of Gram-negative bacteria is mediated by a druggable OM translocon consisting of a beta-barrel membrane protein, LptD, and a lipoprotein, LptE. The beta-barrel assembly machinery (BAM) assembles LptD together with LptE to form a plug-and-barrel structure. In the enterobacterium Escherichia coli, formation of two native disulfide bonds in LptD controls LPS translocon activation. Here we report the discovery of LptM (formerly YifL), a conserved lipoprotein that assembles together with LptD and LptE at the BAM complex. We demonstrate that LptM stabilizes a conformation of LptD that can efficiently acquire native disulfide bonds and be released as mature LPS translocon by the BAM complex. Inactivation of LptM causes the accumulation of non-natively oxidized LptD, making disulfide bond isomerization by DsbC become essential for viability. Our structural prediction and biochemical analyses indicate that LptM binds to sites in both LptD and LptE that are proposed to coordinate LPS insertion into the OM. These results suggest that, by mimicking LPS binding, LptM facilitates oxidative maturation of LptD, thereby activating the LPS translocon.

2023-10-11 | PXD041774 | Pride

HDX-MS of NicA2 and a NicA2 variant with increased activity

Project description:Here we have used HDX-MS to investigate the change in structure/dynamics in NicA2 and a variant with increased activity (v321) that was generated using directed evolution

2023-11-16 | PXD037151 | Pride

Affimer reagents as tools to modulate GPVI-ligand interactions

Project description:We have isolated Affimers that bind to GPVI and characterized their effect on receptor function. An affimer that binds specifically to dimeric GPVI was identified as a novel tool to detect dimeric GPVI. The binding sites of the different Affimers were mapped using HDX-MS, revealing that they interact with functional regions for regulating collagen binding and dimerization.

2024-10-01 | PXD046982 | Pride

Fusidic acid resistance through changes in the dynamics of EF-G

Project description:HDX-MS was used to study the binding of FusB to EF-G

2020-10-15 | PXD017491 | Pride

Hydrogen-deuterium exchange mass spectrometry analysis of the CDK2-cyclin A-CDC25A complex

Project description:The cell division cycle 25 phosphatases CDC25A, B and C regulate cell cycle transitions by dephosphorylating residues in the conserved glycine-rich loop of cyclin-dependent protein kinases (CDKs) to activate CDK activity. Here, we present HDX-MS data to complement the cryogenic-electron microscopy (cryo-EM) structure of CDK2-cyclin A in complex with CDC25A, providing a detailed structural analysis of the overall complex architecture and key protein-protein interactions that underpin this 86 kDa complex. This work improves our understanding of the roles of CDC25 phosphatases in CDK regulation and may inform the development of CDC25-targeting anticancer strategies.

2024-05-29 | PXD050866 | Pride

Conformational dynamics of the human serotonin transporter during substrate and drug binding

Project description:The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs. Our results reveal significant changes in dynamics in regions TM1, EL3, EL4, and TM12 upon binding co-transported ions (Na+/K+) and ligand-mediated changes in TM1, EL3 and EL4 upon binding 5-HT, the drugs S-citalopram, cocaine and ibogaine. Our results provide a comprehensive direct view of the conformational response of SERT upon binding both biologically relevant substrate/ions and ligands of pharmaceutical interest, thus advancing our understanding of the structure-function relationship in SERT.

2019-05-15 | PXD013750 | Pride