PXD040460

PXD040460 is an original dataset announced via ProteomeXchange.

Title	Interaction of human eIF5A and DHS K329A variant studied by HDX-MS
Description	Hypusination is a unique post-translational modification of the eukaryotic translation factor 5A (eIF5A) that is essential for overcoming ribosome stalling at polyproline sequence stretches. The initial step of hypusination, the formation of deoxyhypusine, is catalyzed by deoxyhypusine synthase (DHS), however, the molecular details of the DHS-mediated reaction remained elusive. Recently, patient-derived variants of DHS and eIF5A have been linked to rare neurodevelopmental disorders. Here, we present the cryo-EM structure of the human eIF5A-DHS complex at 2.8Å resolution and a crystal structure of DHS trapped in the key reaction transition state. Furthermore, we show that disease-associated DHS variants influence the complex formation and hypusination efficiency. Hence, our work dissects the molecular details of the deoxyhypusine synthesis reaction and reveals how clinically-relevant mutations affect this crucial cellular process.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:51.482.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wieland Steinchen
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; 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	2023-02-27 06:16:57	ID requested
1	2023-05-10 15:46:32	announced
⏵ 2	2023-11-14 08:47:54	announced	2023-11-14: Updated project metadata.

W, ą, tor E, Wilk P, Biela A, Rawski M, Zak KM, Steinchen W, Bange G, Glatt S, Grudnik P, Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders. Nat Commun, 14(1):1698(2023) [pubmed]

submitter keyword: eIF5A,HDX-MS, Synapt-G2 Si, DHS K329A variant

Gert Bange
contact affiliation	Philipps-University Marburg Department of Chemistry & Center for Synthetic Microbiology (SYNMIKRO) Karl-von-Frisch-Straße 14 35043 Marburg GERMANY
contact email	gert.bange@synmikro.uni-marburg.de
lab head
Wieland Steinchen
contact affiliation	Philipps-University Marburg, Department of Chemistry & SYNMIKRO, Hans-Meerwein-Straße, 35043 Marburg, GERMANY
contact email	wieland.steinchen@synmikro.uni-marburg.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/2023/05/PXD040460

PRIDE project URI

• PRIDE
  1. PXD040460
     1. Label: PRIDE project
     2. Name: Interaction of human eIF5A and DHS K329A variant studied by HDX-MS