PXD039684

PXD039684 is an original dataset announced via ProteomeXchange.

Title	The Trypanosoma brucei MISP family of invariant proteins are co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector
Description	Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the metacyclic expression of invariant surface antigens. Proteomics analyses of saliva from T. brucei-infected flies identified, in addition to VSG and Brucei Alanine-Rich Protein (BARP) peptides, a family of GPIanchored surface proteins herein named Metacyclic Invariant Surface Proteins (MISP). The MISP family is encoded by five paralog genes with >80% protein identity, which are exclusively expressed by salivary gland stages of the parasite and peak in metacyclic stage, as shown by confocal microscopy and immuno-high resolution scanning electron microscopy. Crystallographic analysis of a MISP isoform (MISP360) and a high confidence model of BARP revealed a triple helical bundle architecture commonly found in other trypanosome surface proteins. Molecular modelling combined with live fluorescent microscopy suggests that MISP N-termini are extended above the VSG coat. However, vaccination with recombinant MISP360 isoform did not protect mice against a T. brucei infectious tsetse bite. Lastly, both RNAi knock down and CRISPR-Cas9-driven knock out of all MISP paralogues suggest they are not essential for parasite development in the tsetse vector. We speculate that MISP may be relevant during trypanosome inoculation or establishment in the vertebrate’s skin.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:16.573.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Douglas Lamont
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-26 02:45:08	ID requested
1	2023-05-10 14:05:09	announced
⏵ 2	2023-11-14 08:47:17	announced	2023-11-14: Updated project metadata.

Casas-Sanchez A, Ramaswamy R, Perally S, Haines LR, Rose C, Aguilera-Flores M, Portillo S, Verbeelen M, Hussain S, Smithson L, Yunta C, Lehane MJ, Vaughan S, van den Abbeele J, Almeida IC, Boulanger MJ, Acosta-Serrano Á, The Trypanosoma brucei MISP family of invariant proteins is co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector. PLoS Pathog, 19(3):e1011269(2023) [pubmed]

submitter keyword: proteomics, mass spectrometry, crystal structure, metacyclic,Trypanosoma brucei, tsetse, MISP, GPI

Dr Alvaro Acosta Serrano
contact affiliation	Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA UK
contact email	alvaro.acosta-serrano@lstmed.ac.uk
lab head
Douglas Lamont
contact affiliation	School of Life Sciences
contact email	d.j.lamont@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039684
     1. Label: PRIDE project
     2. Name: The Trypanosoma brucei MISP family of invariant proteins are co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector