PXD040499

PXD040499 is an original dataset announced via ProteomeXchange.

Title	Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation
Description	The MAP kinase p38α is a central component of signalling in inflammation and the immune response, and is therefore an important drug target. Little is known about the molecular mechanism of its activation by double-phosphorylation from MAP2Ks, due to the challenge of trapping a transient and dynamic hetero-kinase complex. Here, we applied a multidisciplinary approach to generate the first structure of p38α in complex with its MAP2K MKK6 and understand the activation mechanism. Integrating cryo-EM with MD simulations and in cellulo experiments, we demonstrate a dynamic, multi-step, phosphorylation mechanism, reveal new catalytically relevant interactions, and show that MAP2K disordered N-termini determine pathway specificity. Our work captures, for the first time, a fundamental step of cell signalling: a kinase phosphorylating its downstream target kinase
HostingRepository	PRIDE
AnnounceDate	2023-08-31
AnnouncementXML	Submission_2023-08-31_08:45:44.977.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD040499
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	OscarVadas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-28 06:56:41	ID requested
⏵ 1	2023-08-31 08:45:45	announced

10.6019/PXD040499;

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: Kinases,HDX-MS, Molecular Dynamics, MAPK, Cryo-EM, MKK6

OscarVadas
contact affiliation	Faculty of Medicine, Platform of services, Protein expression and purification, University of Geneva, 1211 Geneva, Switzerland
contact email	oscar.vadas@unige.ch
lab head
OscarVadas
contact affiliation	University of Geneva, Faculty of Medicine
contact email	oscar.vadas@unige.ch
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/2023/08/PXD040499

PRIDE project URI

• PRIDE
  1. PXD040499
     1. Label: PRIDE project
     2. Name: Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation