PXD015778

PXD015778 is an original dataset announced via ProteomeXchange.

Title	Architecture of human Rag GTPase heterodimers and their complex with mTORC1
Description	The Rag GTPases recruit the master kinase mTORC1 to lysosomes to regulate cell growth and proliferation in response to amino acid availability. The nucleotide state of Rag heterodimers is critical for their association with mTORC1. Our cryo-EM structure of RagA/RagC in complex with mTORC1 shows the details of RagA/C binding to the RAPTOR subunit of mTORC1 and explains why only the RagAGTP/RagCGDP nucleotide state binds mTORC1. Previous kinetic studies suggested that GTP binding to one Rag locks the heterodimer to prevent GTP binding to the other. Our crystal structures and dynamics show the mechanism for this locking, and explain how oncogenic hotspot mutations disrupt this process. In contrast to allosteric activation by RHEB, Rag heterodimer binding does not change mTORC1 conformation and activates mTORC1 by targeting it to lysosomes.
HostingRepository	PRIDE
AnnounceDate	2019-10-11
AnnouncementXML	Submission_2019-10-25_06:44:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Glenn Masson
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	2019-10-10 07:01:45	ID requested
1	2019-10-11 05:19:32	announced
⏵ 2	2019-10-25 06:44:17	announced	2019-10-25: Updated publication reference for PubMed record(s): 31601764.

Anandapadamanaban M, Masson GR, Perisic O, Berndt A, Kaufman J, Johnson CM, Santhanam B, Rogala KB, Sabatini DM, Williams RL, Architecture of human Rag GTPase heterodimers and their complex with mTORC1. Science, 366(6462):203-210(2019) [pubmed]

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

submitter keyword: HDX-MS, mTORC1, RagA, RagC

Glenn Robert Masson
contact affiliation	Medical Research Council Laboratory of Molecular Biology
contact email	gmasson@mrc-lmb.cam.ac.uk
lab head
Glenn Masson
contact affiliation	MRC Laboratory of Molecular Biology
contact email	gmasson@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/2019/10/PXD015778

PRIDE project URI

• PRIDE
  1. PXD015778
     1. Label: PRIDE project
     2. Name: Architecture of human Rag GTPase heterodimers and their complex with mTORC1