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Dissecting the malaria interactome

ABSTRACT: To identify malaria protein interactions systematically we combined blue native polyacrylamide electrophoresis fractionation with quantitative mass spectrometry and machine learning. Our integrative approach identified over twenty thousand protein interactions in Plasmodium schizonts, organized into 600 complexes, the majority of which are novel, and generated a high-confidence Plasmodium protein interaction network.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: James Wright

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD009039 | Pride | 2019-08-06

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	CH09BN_MQresults.zip	Other
	CH10AN_MQresults.zip	Other
	CH12AN_MQresults.zip	Other
	CH_BERG_ONE_21_MQresults.zip	Other
	CH_BERG_ZERO_20_MQresults.zip	Other

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Publications

Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.

Hillier Charles C Pardo Mercedes M Yu Lu L Bushell Ellen E Sanderson Theo T Metcalf Tom T Herd Colin C Anar Burcu B Rayner Julian C JC Billker Oliver O Choudhary Jyoti S JS

Cell reports 20190801 6

Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing Plasmodium parasites being uncharacterized. We report a large-scale protein interaction network in Plasmodium schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species, id ...[more]

PMID: 31390575

Similar Datasets

Dissecting the malaria interactome

Project description:To identify malaria protein interactions systematically we combined blue native polyacrylamide electrophoresis fractionation with quantitative mass spectrometry and machine learning. Our integrative approach identified over twenty thousand protein interactions in Plasmodium schizonts, organized into 600 complexes, the majority of which are novel, and generated a high-confidence Plasmodium protein interaction network.

2019-08-06 | PXD010117 | Pride

The role of actin II in the mosquito stages of Plasmodium berghei

Project description:The aim of this work is to characterize the Plasmodium berghei actin II during mosquito stages with special focus on post-translational modification of histidine.

2023-02-16 | PXD033378 | Pride

Transcriptomic analysis of Anopheles stephensi salivary glands during Plasmodium berghei infection

Project description:RNA-seq of Anopheles stephensi salivary glands during Plasmodium berghei infection

2015-11-05 | E-MTAB-3964 | biostudies-arrayexpress

Proteomic analysis of the Plasmodium male gamete reveals a key role for glycolysis in flagellar motility

Project description:Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathways of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. To gain more insight into male gamete, we performed the first proteomic analysis of purified Plasmodium berghei microgametes. We recovered 615 proteins, which include all male gamete proteins described thus far. Amongst the most abundant proteins were the 11 enzymes of the glycolytic pathway. We localized the hexose transporter to the gamete plasma membrane and show that microgamete motility can be suppressed effectively by inhibitors of this transporter, and of the glycolytic pathway. Taken together, these results suggest that glycolysis is the exclusive source of energy for microgamete motility. Considering that this proteome provides a unique platform for the understanding of the original features of the male gamete, we discuss not only the mitochondria-independent energy metabolism but also flagellar structure and intra-flagellar transport-independent assembly, another divergent feature of these cells.

2014-08-18 | PXD001163 | Pride

RNA-seq analyses of gene expression changes in the salivary glands of Anopheles gambiae elicited by Plasmodium berghei infection

Project description:Salivary glands are the only mosquito tissue invaded by Plasmodium sporozoites being a key stage for the effective parasite transmission and maturation, making knowledge regarding Anopheles sialome highly relevant to understand this process. In this study, we report for the first time a transcriptomic analysis using RNA-seq of An. gambiae infected by P. berghei.

2015-06-01 | E-MTAB-3415 | biostudies-arrayexpress

Deep profiling of the novel intermediate-size noncoding RNAs in intraerythrocytic Plasmodium falciparum

Project description:Intermediate-size noncoding RNAs (is-ncRNAs) have been shown to play important regulatory roles in the development of several eukaryotic organisms. However, they have not been thoroughly explored in Plasmodium falciparum, which is the most virulent malaria parasite infecting human being. By using Illumina/Solexa paired-end sequencing of an is-ncRNA-specific library, we performed a systematic identification of novel is-ncRNAs in intraerythrocytic P. falciparum, strain 3D7. A total of 1,198 novel is-ncRNA candidates, including antisense, intergenic, and intronic is-ncRNAs, were identified. Bioinformatics analyses showed that the intergenic is-ncRNAs were the least conserved among different Plasmodium species, and antisense is-ncRNAs were more conserved than their sense counterparts. Twenty-two novel snoRNAs were identified, and eight potential novel classes of P. falciparum is-ncRNAs were revealed by clustering analysis. The expression of randomly selected novel is-ncRNAs was confirmed by RT-PCR and northern blotting assays. An obvious different expressional profile of the novel is-ncRNA between the early and late intraerythrocytic developmental stages of the parasite was observed. The expression levels of the antisense RNAs correlated with those of their cis-encoded sense RNA counterparts, suggesting that these is-ncRNAs are involved in the regulation of gene expression of the parasite. In conclusion, we accomplished a deep profiling analysis of novel is-ncRNAs in P. falciparum, analysed the conservation and structural features of these novel is-ncRNAs, and revealed their differential expression patterns during the development of the parasite. These findings provide important information. One RNA sample (50-500 nt ) from the mixed intraerythrocytic stage of P. falciparum 3D7, subjected to Illumina/Solexa paired-end sequencing

2014-03-30 | E-GEOD-45172 | biostudies-arrayexpress

Proteomics analysis of P. knowlesi mutants

Project description:Mass spectrometry-based identification of mutated and wild-type Plasmodium falciparum lysyl tRNA synthetase (PfKRS) in Plasmodium knowlesi.

2024-08-13 | PXD049335 | Pride

Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

Project description:This SuperSeries is composed of the following subset Series: GSE25878: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription (expression) GSE25879: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription (CGH) Refer to individual Series

2010-12-07 | E-GEOD-25883 | biostudies-arrayexpress

Mechanochemical tuning of a kinesin motor essential for malaria parasite transmission

Project description:Kinesins are a superfamily of molecular motors that undertake ATP-dependent microtubule-based movement or regulate microtubule dynamics. Plasmodium species, which cause malaria and kill hundreds of thousands annually, encode ~9 kinesins in their genomes. Of these, two – kinesin-8B and kinesin-8X - are canonically classified as kinesin-8s, which in other eukaryotes typically modulate microtubule dynamics. Unexpectedly, Plasmodium kinesin-8B is required for development of the flagellated male gamete in the mosquito host, and its absence completely blocks parasite transmission. To understand the molecular basis of kinesin-8B’s essential role, we characterised the in vitro properties of the kinesin-8B motor domains from P. berghei and P. falciparum. Both motors drive plus-end directed ATP-dependent microtubule gliding, but also catalyse ATP-dependent microtubule depolymerisation. We determined the microtubule-bound structures of these motors using cryo-electron microscopy. P. berghei and P. falciparum kinesin-8B exhibit a very similar mode of microtubule interaction, in which Plasmodium-distinct sequences at the microtubule-kinesin interface influence motor function. Intriguingly, however, P. berghei kinesin-8B exhibits a non-canonical structural response to ATP analogue binding such that neck linker docking is not induced. Nevertheless, the neck linker region is absolutely required for motility and depolymerisation activities of these motors. Taken together, these data suggest that the mechanochemistry of Plasmodium kinesin-8Bs has been functionally tuned to efficiently contribute to flagella formation.

2022-12-05 | PXD037474 | Pride

The proteomes of plasmodium falciparum mature male and female gametocytes

Project description:Gametocytes are obligate for the transmission of malaria parasite to mosquito. This study reports the first comprehensive proteomes of accurately separated mature male and female Plasmodium falciparum gametocytes using a transgenic line. the proteomes revealed significant differences that are consistent with the divergent functions of the two sexes. While the male proteome is enriched in proteins associated with flagella and genome replication, the female proteome is more abundant in proteins involved in metabolism, translation and organellar functions.

2017-01-30 | PXD003556 | Pride