PXD047538

PXD047538 is an original dataset announced via ProteomeXchange.

Title	Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B
Description	HDX-MS of R15B and it's interactions with trimeric eIF2 substrate. Here we integrated diverse approaches to elucidate how the PP1 non-catalytic subu-nit PPP1R15B (R15B) captures its full trimeric eIF2 substrate. We found that the substrate recruitment module of R15B is largely disordered with three short helical elements, H1, H2 and H3. H1 and H2 form a clamp that grasps the substrate in a re-gion remote from the phosphorylated residue. A homozygous N423D variant, adja-cent to H1, reducing substrate binding and dephosphorylation was discovered in a ra-re syndrome with microcephaly, development delay and intellectual disability. These findings explain how R15B captures its 125 kDa substrate by binding the far end of the complex relative to the phospho-site to present it for dephosphorylation by PP1, a paradigm of broad relevance.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:41:31.279.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tomos Morgan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-05 07:30:26	ID requested
1	2024-05-22 12:28:28	announced
⏵ 2	2024-10-22 06:41:37	announced	2024-10-22: Updated project metadata.

Fatalska A, Hodgson G, Freund SMV, Maslen SL, Morgan T, Thorkelsson SR, van Slegtenhorst M, Lorenz S, Andreeva A, Kaat LD, Bertolotti A, Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B. Mol Cell, 84(3):506-521.e11(2024) [pubmed]

10.1016/j.molcel.2023.12.011;

submitter keyword: HDX-MS, HD-MS

Anne Bertolotti
contact affiliation	Medical Research Council - Laboratory of Molecular Biology
contact email	aberto@mrc-lmb.cam.ac.uk
lab head
Tomos Morgan
contact affiliation	MRC-LMB
contact email	tmorgan@mrc-lmb.cam.ac.uk
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/2024/05/PXD047538

PRIDE project URI

• PRIDE
  1. PXD047538
     1. Label: PRIDE project
     2. Name: Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B