PXD048979-2

PXD048979 is an original dataset announced via ProteomeXchange.

Title	Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites
Description	The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:47:21.754.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Helen Flynn
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-29 08:14:23	ID requested
1	2024-06-24 07:20:23	announced
⏵ 2	2024-10-22 06:47:22	announced	2024-10-22: Updated project metadata.

10.1371/JOURNAL.PPAT.1012360.;

submitter keyword: phosphorylation, cGMP-dependent protein kinase,malaria, genetics, Plasmodium falciparum

Mark Skehel
contact affiliation	Head of Proteomics The Francis Crick Institute 1 Midland Road London NW1 1AT U.K.
contact email	mark.skehel@crick.ac.uk
lab head
Helen Flynn
contact affiliation	The Francis Crick Institute
contact email	helen.flynn@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048979
     1. Label: PRIDE project
     2. Name: Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites