Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tension mediated mechanical activation and pocket delipidation lead to an analogous MscL channel state

ABSTRACT: We present HDX-MS data of WT and L89W TbMscL to interrogate the mechanism of molecular activation in this mechanosensitive channel.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mycobacterium Tuberculosis Eai/osdd271

SUBMITTER: Antonio Calabrese

LAB HEAD: Antonio Calabrese

PROVIDER: PXD021983 | Pride | 2022-06-07

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state.

Wang Bolin B Lane Benjamin J BJ Kapsalis Charalampos C Ault James R JR Sobott Frank F El Mkami Hassane H Calabrese Antonio N AN Kalli Antreas C AC Pliotas Christos C

Structure (London, England : 1993) 20220104 4

The mechanosensitive ion channel of large conductance MscL gates in response to membrane tension changes. Lipid removal from transmembrane pockets leads to a concerted structural and functional MscL response, but it remains unknown whether there is a correlation between the tension-mediated state and the state derived by pocket delipidation in the absence of tension. Here, we combined pulsed electron paramagnetic resonance spectroscopy and hydrogen-deuterium exchange mass spectrometry, coupled w ...[more]

PMID: 34986323

Similar Datasets

Mapping of a N-terminal alpha-helix domain required for human PINK1 stabilisation, Serine228 autophosphorylation and activation in cells

Project description:Comparative hydrogen deuterium exchange mass spectrometry of WT and I507A mutant for above titled manuscript.

2022-02-17 | PXD030382 | Pride

Analysis of the PcrA-RNA polymerase complex reveals a helicase interaction motif and a role for PcrA/UvrD helicase in the suppression of R-loops

Project description:HDX-MS was used to study the binding of PcrA to RNA polymerase

2021-07-20 | PXD025332 | Pride

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

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

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

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

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

HDX-MS data of trigger factor and GAPDH binding

Project description:We present HDX-MS data of the trigger factor:GAPDH complex to define the interaction sites for GAPDH on trigger factor and the structure of GAPDH in the bound state.

2022-06-07 | PXD029364 | 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

Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides

Project description:Dampening functional levels of the mitochondrial deubiquitylating enzyme USP30 has been suggested as an effective therapeutic strategy against neurodegenerative disorders such as Parkinson’s Disease. USP30 inhibition may counteract the deleterious effects of impaired turnover of damaged mitochondria which is inherent to both familial and sporadic forms of the disease. Small-molecule inhibitors targeting USP30 are currently in development, but little is known about their precise nature of binding to the protein. We have integrated biochemical and structural approaches to gain novel mechanistic insights into USP30 inhibition by a small-molecule benzosulfonamide containing compound, 39. Activity-based protein profiling (ABPP) mass spectrometry confirmed target engagement, the high selectivity, and potency of 39 for USP30 against 49 other deubiquitylating enzymes in a neuroblastoma cell line. In vitro characterization of 39 enzyme kinetics infers slow and tight binding behavior, which is comparable with features of covalent modification of USP30. Finally, we blended hydrogen-deuterium exchange mass spectrometry and computational docking to elucidate the molecular architecture and geometry of USP30 complex formation with 39, identifying structural rearrangements at the cleft of the USP30 thumb and palm subdomains. These studies suggest that 39 binds to the thumb-palm cleft that guides the ubiquitin C-terminus into the active site, thereby preventing ubiquitin binding and isopeptide bond cleavage, and confirming its importance in the inhibitory process. Our data will pave the way for the design and development of next-generation inhibitors targeting USP30 and associated deubiquitinylases.

2023-10-24 | PXD041582 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data