PXD022944

PXD022944 is an original dataset announced via ProteomeXchange.

Title	Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization
Description	Upon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.
HostingRepository	PRIDE
AnnounceDate	2021-08-16
AnnouncementXML	Submission_2021-08-26_06:30:11.490.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Underbakke
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-07 00:28:07	ID requested
1	2021-08-16 08:23:25	announced
⏵ 2	2021-08-26 06:30:12	announced	2021-08-26: Updated publication reference for PubMed record(s): 34400635.

Agnew C, Ayaz P, Kashima R, Loving HS, Ghatpande P, Kung JE, Underbakke ES, Shan Y, Shaw DE, Hata A, Jura N, Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization. Nat Commun, 12(1):4950(2021) [pubmed]

submitter keyword: ALK2, BMPR2, HDX-MS

Eric S. Underbakke
contact affiliation	Roy J. Carver Dept. of Biochemistry, Biophysics, and Molecular Biology Iowa State University Ames, IA USA
contact email	esu@iastate.edu
lab head
Eric Underbakke
contact affiliation	Iowa State University
contact email	esu@iastate.edu
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/2021/08/PXD022944

PRIDE project URI

• PRIDE
  1. PXD022944
     1. Label: PRIDE project
     2. Name: Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization