PXD025209 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Structure of the phosphoinositide 3-kinase p110-p101 complex reveals molecular mechanism of GPCR activation |
Description | The class IB phosphoinositide 3-kinase (PI3K), PI3K, is a master regulator of immune cell function, and is a promising drug target for both inflammatory diseases and cancer. Critical to PI3K function is the association of the p110 catalytic subunit to either a p101 or p84 regulatory subunit, which mediates regulation by G-protein coupled receptors (GPCRs). Here, we report the first structure of a heterodimeric PI3K complex, p110-p101. This structure revealed a unique mode of assembly of catalytic and regulatory subunits distinct from that of other class I PI3K complexes. Multiple oncogenic mutations mapped to these novel interfaces led to increased activation by G. p101 mediates activation through its G binding domain, recruiting the complex to the membrane and allowing for engagement of a secondary site in p110. A nanobody that specifically binds to this p101-G interface blocks activation providing a novel tool to study p101-specific signaling events in vivo. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:29:31.741.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | John Burke |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | impact HD |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-04-06 06:14:53 | ID requested | |
1 | 2021-09-22 10:21:34 | announced | |
⏵ 2 | 2024-10-22 05:29:32 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1126/sciadv.abj4282; |
Rathinaswamy MK, Dalwadi U, Fleming KD, Adams C, Stariha JTB, Pardon E, Baek M, Vadas O, DiMaio F, Steyaert J, Hansen SD, Yip CK, Burke JE, -p101 complex reveals molecular mechanism of GPCR activation. Sci Adv, 7(35):(2021) [pubmed] |
Keyword List
submitter keyword: HDX, cryo-EM, GPCR,PIK3g |
Contact List
Dr. John E Burke |
contact affiliation | University of Victoria |
contact email | jeburke@uvic.ca |
lab head | |
John Burke |
contact affiliation | University of Victoria |
contact email | jeburke@uvic.ca |
dataset submitter | |
Full Dataset Link List
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/2021/09/PXD025209 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025209
- Label: PRIDE project
- Name: Structure of the phosphoinositide 3-kinase p110-p101 complex reveals molecular mechanism of GPCR activation