PXD027295

PXD027295 is an original dataset announced via ProteomeXchange.

Title	De Novo Design of Tyrosine and Serine Kinase Driven Protein Switches
Description	: Kinases play central roles in signaling cascades, relaying information from the outside to the inside of mammalian cells1. De novo designed protein switches capable of interfacing with tyrosine kinase signaling pathways would open new avenues for controlling cellular behavior, but to date no such systems have been described. Here we describe the de novo design of two classes of protein switches which link phosphorylation by both tyrosine and serine kinases to protein-protein association. In the first class, protein-protein association drives kinase phosphorylation; addition of a designed co-regulator induces the phosphorylation of the ITAM motif central to T-cell signaling2. In the second class, kinase phosphorylation drives protein-protein association; we describe systems in which kinase action drives reconstitution of GFP fluorescence from fragments and the inhibition of the protease calpain. The designed switches are reversible and function in vitro and in cells with up to 40-fold activation of switching by phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2022-05-27
AnnouncementXML	Submission_2022-05-27_02:51:28.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Johnson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-14 07:13:39	ID requested
⏵ 1	2022-05-27 02:51:29	announced

Woodall NB, Weinberg Z, Park J, Busch F, Johnson RS, Feldbauer MJ, Murphy M, Ahlrichs M, Yousif I, MacCoss MJ, Wysocki VH, El-Samad H, Baker D, De novo design of tyrosine and serine kinase-driven protein switches. Nat Struct Mol Biol, 28(9):762-770(2021) [pubmed]

submitter keyword: kinase, switch, designed proteins

David Baker
contact affiliation	Department of Biochemistry, University of Washington, Seattle, WA, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA Institute for Protein Design, University of Washington, Seattle, WA, USA
contact email	dabaker@uw.edu
lab head
Richard Johnson
contact affiliation	University of Washington
contact email	rj8@uw.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/2022/04/PXD027295

PRIDE project URI

• PRIDE
  1. PXD027295
     1. Label: PRIDE project
     2. Name: De Novo Design of Tyrosine and Serine Kinase Driven Protein Switches