{"doi":"10.3389/fcimb.2022.924424","title":"Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion","abstract":"<jats:p>Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during <jats:italic>Plasmodium falciparum</jats:italic> invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein–protein interaction (PPI) network-based molecular machinery. Here, we used an integrated <jats:italic>in silico</jats:italic> analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in <jats:italic>P. falciparum</jats:italic>, predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP’s interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed <jats:italic>via</jats:italic> synergistic inhibition in <jats:italic>P. falciparum</jats:italic> invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion <jats:italic>via</jats:italic> glideosome assembly protein myosin A in <jats:italic>P. falciparum</jats:italic>. These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics.</jats:p>","journal":"Frontiers in Cellular and Infection Microbiology","year":2022,"id":595806,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1525855,"name":"Geeta Kumari","orcid":null,"position":1,"is_corresponding":false},{"id":1525856,"name":"Soumyadeep Mukherjee","orcid":null,"position":2,"is_corresponding":false},{"id":1200516,"name":"Devasahayam Arokia Balaya Rex","orcid":null,"position":3,"is_corresponding":false},{"id":1525857,"name":"Shreeja Biswas","orcid":null,"position":4,"is_corresponding":false},{"id":1167124,"name":"Preeti Maurya","orcid":"0000-0003-1181-3608","position":5,"is_corresponding":false},{"id":1525858,"name":"Susendaran Ravikumar","orcid":null,"position":6,"is_corresponding":false},{"id":1525859,"name":"Nutan Gupta","orcid":null,"position":7,"is_corresponding":false},{"id":1525860,"name":"Akhilesh Kumar Kushawaha","orcid":null,"position":8,"is_corresponding":false},{"id":389729,"name":"Raj Kumar Sah","orcid":null,"position":9,"is_corresponding":false},{"id":1525861,"name":"Ayushi Chaurasiya","orcid":null,"position":10,"is_corresponding":false},{"id":1525862,"name":"Jhalak Singhal","orcid":null,"position":11,"is_corresponding":false},{"id":960315,"name":"Niharika Singh","orcid":"0000-0001-9177-4316","position":12,"is_corresponding":false},{"id":1525864,"name":"Shikha Kaushik","orcid":null,"position":13,"is_corresponding":false},{"id":74783,"name":"T. 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Keshava Prasad","orcid":null,"position":14,"is_corresponding":false},{"id":389013,"name":"Soumya Pati","orcid":"0000-0003-4631-4753","position":15,"is_corresponding":false},{"id":708072,"name":"Anand Ranganathan","orcid":null,"position":16,"is_corresponding":false},{"id":389016,"name":"Shailja Singh","orcid":"0000-0001-5286-6605","position":17,"is_corresponding":false},{"id":1525854,"name":"Zille Anam","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion","abstract":"<jats:p>Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during <jats:italic>Plasmodium falciparum</jats:italic> invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein–protein interaction (PPI) network-based molecular machinery. Here, we used an integrated <jats:italic>in silico</jats:italic> analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in <jats:italic>P. falciparum</jats:italic>, predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP’s interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed <jats:italic>via</jats:italic> synergistic inhibition in <jats:italic>P. falciparum</jats:italic> invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion <jats:italic>via</jats:italic> glideosome assembly protein myosin A in <jats:italic>P. falciparum</jats:italic>. These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36250062","pmcid":"PMC9556994","openalex_id":null,"authors":[],"funders":[{"funder_name":"Department of Science and Technology, Ministry of Science and Technology, India","grant_id":"","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3389/fcimb.2022.924424","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fcimb.2022.924424/full","host_type":"publisher"},{"url":"https://doaj.org/article/17bf1b44800d4080a9db15302f487ad6","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9556994","host_type":"repository"},{"url":"https://www.frontiersin.org/articles/10.3389/fcimb.2022.924424/pdf","host_type":"Unpaywall"},{"url":"https://europepmc.org/articles/PMC9556994","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9556994?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Humans","Plasmodium falciparum","Malaria, Falciparum","Nonmuscle Myosin Type IIA","Cytoskeletal Proteins","Membrane Proteins","Proteome","Protozoan Proteins","Antimalarials","Phosphorylation","Lipoylation"],"keywords":["Malaria","Plasmodium falciparum","Post-translational modifications","crosstalk","Myosin A Tail Interacting Protein (Mtip)"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gca"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:54:24.048857Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}