PXD016338

PXD016338 is an original dataset announced via ProteomeXchange.

Title	Biophysical basis of cellular multi-specificity encoded in a model molecular switch
Description	Molecular switches are central to many cellular networks, enabling signal processing via interactions with molecules that write, erase, or read the active state of the switch. One switch protein can independently regulate distinct processes, but the molecular mechanisms enabling this functional multi-specificity remain unclear. Here we integrate system-scale cellular and biophysical measurements to study how a paradigm switch, the small GTPase Ran/Gsp1, achieves its functional multi-specificity. We make targeted point mutations to individual interactions of Ran/Gsp1 and show through genetic and physical interaction mapping that Ran/Gsp1 interface perturbations have widespread cellular consequences that cluster by biological processes but, unexpectedly, not by the targeted interactions. Instead, the cellular consequences of the interface mutations group by their biophysical effects on kinetic parameters of the GTPase switch cycle, and cycle kinetics are allosterically tuned by distal interface mutations. We propose that the functional multi-specificity of Ran/Gsp1 is explained by a differential sensitivity of biological processes to different kinetic parameters of the Gsp1 switch cycle, and that Gsp1 switch readers binding to the sites of distal mutations can also act as allosteric writers and erasers of the switch cycle. Similar mechanisms may underlie biological regulation by other GTPases and biological switches in general.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:03:51.695.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Danielle Swaney
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-19 04:12:06	ID requested
1	2020-05-18 00:00:40	announced
⏵ 2	2024-10-22 05:03:52	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: PPIs,yeast

Nevan Krogan
contact affiliation	Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA The J. David Gladstone Institutes, San Francisco, CA, USA.
contact email	daniswan@gmail.com
lab head
Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
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/2020/05/PXD016338

PRIDE project URI

• PRIDE
  1. PXD016338
     1. Label: PRIDE project
     2. Name: Biophysical basis of cellular multi-specificity encoded in a model molecular switch