PXD021843-1

PXD021843 is an original dataset announced via ProteomeXchange.

Title	The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion
Description	Red blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane then seals and pinches off behind the parasite through an unknown mechanism, enclosing it within the RBC. During invasion, several merozoite surface proteins are shed by a membrane-bound protease called SUB2. Here we show that genetic depletion of SUB2 abolishes shedding of a range of parasite proteins, identifying previously unrecognized SUB2 substrates. Interaction of SUB2-null merozoites with RBCs leads to either successful entry but developmental arrest, or abortive invasion with rapid RBC lysis. Selective failure to shed the most abundant SUB2 substrate, MSP1, reduces intracellular replication, whilst conditional ablation of the substrate AMA1 produces host RBC lysis. We conclude that SUB2 activity is critical for the correct functioning of merozoite surface protein substrates and for host RBC membrane sealing following parasite internalisation.
HostingRepository	PRIDE
AnnounceDate	2020-11-27
AnnouncementXML	Submission_2020-11-26_22:59:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Howell
SpeciesList	scientific name: Plasmodium falciparum 3D7; NCBI TaxID: 36329; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-05 07:21:44	ID requested
⏵ 1	2020-11-26 22:59:34	announced

Dataset with its publication pending

submitter keyword: SUB2, orbitrap, protease, malaria

Bram Snijders
contact affiliation	Head of Proteomics facility
contact email	bram.snijders@crick.ac.uk
lab head
Steven Howell
contact affiliation	Francis Crick Institute
contact email	steven.howell@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021843
     1. Label: PRIDE project
     2. Name: The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion