Dataset Information

Surveyance of apparent proteome unfolding curves via thiol labelling under HSP70 inhibition

ABSTRACT: Census of apparent proteome unfolding curves following urea denaturation in cell lysate derived from control of VER155008-treated N2a cells using thiol reactivity probe tetraphenylethene maleimide (TPE-MI).

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Dezerae Cox

LAB HEAD: Danny Hatters

PROVIDER: PXD030567 | Pride | 2022-05-20

REPOSITORIES: Pride

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Publications

Hidden information on protein function in censuses of proteome foldedness.

Cox Dezerae D Ang Ching-Seng CS Nillegoda Nadinath B NB Reid Gavin E GE Hatters Danny M DM

Nature communications 20220414 1

Methods that assay protein foldedness with proteomics have generated censuses of apparent protein folding stabilities in biological milieu. However, different censuses poorly correlate with each other. Here, we show that the reason for this is that methods targeting foldedness through monitoring amino acid sidechain reactivity also detect changes in conformation and ligand binding, which can be a substantial fraction of the data. We show that the reactivity of only one quarter of cysteine or met ...[more]

PMID: 35422070

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Project description:Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets. To better understand its role, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified a total of 1006 gene promoters bound by Arx in transfected neuroblastoma (N2a) cells and in mouse embryonic brain. Some of these promoters were enriched for a sequence very similar to a motif previously identified as Arx-binding motif and approximately 24% of Arx-bound genes were found to show expression changes following Arx overexpression or knock-down. Several of the Arx target genes we identified are known to be important for a variety of functions in brain development, including axonal guidance and synaptic plasticity and some of them suggest new functions for Arx. Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations. N2a cells were transfected with either Arx or the corresponding empty vector. Eight different independent experiments were performed. The 16 samples were randomly distributes on the 2 expression microarrays.

Dataset Information

Surveyance of apparent proteome unfolding curves via thiol labelling under HSP70 inhibition

Publications

Hidden information on protein function in censuses of proteome foldedness.

Similar Datasets

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