PXD012745

PXD012745 is an original dataset announced via ProteomeXchange.

Title	Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP - effect of Mg dataset
Description	Nucleotide triphosphates (NTPs) regulate numerous biochemical processes in cells as (co-)substrates, allosteric modulators, biosynthetic precursors, and signaling molecules1-3. Apart from its roles as energy source fueling cellular biochemistry, adenosine triphosphate (ATP), the most abundant NTP in cells, has been reported to affect macromolecular assemblies, such as protein complexes4,5 and membrane-less organelles6-8. Moreover, both ATP and guanosine triphosphate (GTP) have recently been shown to dissolve protein aggregates9. However, system-wide studies to characterize NTP- interactions under conditions approximating the native cellular environment are lacking, which limits our perspective of the diverse physiological roles of NTPs. Here, we have mapped and quantified proteome-wide NTP-interactions by assessing thermal stability and solubility of proteins using mechanically disrupted cells. Our results reveal diverse biological roles of ATP depending on its concentration. We found that ATP specifically interacts with proteins that utilize it as substrate or allosteric modulator at doses lower than 500 μM, while it affects protein-protein interactions of protein complexes at mildly higher concentrations (between 1-2 mM). At high concentrations (> 2 mM), ATP modulates the solubility state of a quarter of the insoluble proteome, consisting of positively charged, intrinsically disordered, nucleic acid binding proteins, which are part of membrane-less organelles. The extent of solubilization depends on the localization of proteins to different membrane-less organelles. Furthermore, we uncover that ATP regulates protein-DNA interactions of the Barrier to autointegration factor (BANF1). Our data provides the first quantitative proteome-wide map of ATP affecting protein structure and protein complex stability and solubility, providing unique clues on its role in protein phase transitions.
HostingRepository	PRIDE
AnnounceDate	2019-03-11
AnnouncementXML	Submission_2019-04-03_04:35:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nils Kurzawa
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-18 01:22:28	ID requested
1	2019-03-11 15:01:29	announced
⏵ 2	2019-04-03 04:35:10	announced	Updated publication reference for PubMed record(s): 30858367.

Sridharan S, Kurzawa N, Werner T, G, ü, nthner I, Helm D, Huber W, Bantscheff M, Savitski MM, Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP. Nat Commun, 10(1):1155(2019) [pubmed]

curator keyword: Biological

submitter keyword: Jurkat, SPP, ATP

Mikhail M Savitski
contact affiliation	European Molecular Biology Laboratory (EMBL), Genome Biology Unit
contact email	mikhail.savitski@embl.de
lab head
Nils Kurzawa
contact affiliation	EMBL Heidelberg
contact email	nils.kurzawa@embl.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/03/PXD012745

PRIDE project URI

• PRIDE
  1. PXD012745
     1. Label: PRIDE project
     2. Name: Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP - effect of Mg dataset