PXD021873-1

PXD021873 is an original dataset announced via ProteomeXchange.

Title	Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding
Description	VAR2CSA is the placental-malaria specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ~310 kDa ectodomain of VAR2CSA is a multi-domain protein that requires a minimum 12- mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of IRBCs and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria.
HostingRepository	PRIDE
AnnounceDate	2020-12-02
AnnouncementXML	Submission_2020-12-02_06:39:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JagadeeshaPrasad MG
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-07 01:18:31	ID requested
⏵ 1	2020-12-02 06:39:04	announced

Bewley MC, Gautam L, Jagadeeshaprasad MG, Gowda DC, Flanagan JM, Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding. J Biol Chem, 295(52):18589-18603(2020) [pubmed]

ProteomeXchange project tag: Malaria Host-Pathogen Interaction Center (MaHPIC)

submitter keyword: LC-MSMS

John Flangan
contact affiliation	Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033
contact email	jmf27@psu.edu
lab head
JagadeeshaPrasad MG
contact affiliation	Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA17033
contact email	jug1031@psu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021873
     1. Label: PRIDE project
     2. Name: Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding