<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components"^^ . "In 2023, an estimated 263 million malaria cases and 597,000 deaths occurred across 83 countries, with\r\nPlasmodium falciparum being the deadliest malaria parasite (World Health Organization, 2024). A key\r\ndriver of Plasmodium falciparum virulence is cytoadhesion, mediated by antigens such as PfEMP1,\r\npresented on knobs formed on infected red blood cells (iRBCs). These knobs depend on the knobassociated\r\nhistidine-rich protein (KAHRP, PfIT_020006800), exported alongside other parasite proteins\r\nthat remodel iRBCs. This study focuses on two major virulence factors: knob assembly and protein\r\nexport.\r\nUsing alanine scanning, I identified the β-sheet structured region of KAHRP (amino acids 136 to 190)\r\nas essential for knob formation, with alanine substitutions disrupting knob assembly and resulting in a\r\nknobless phenotype. In contrast, mutations in the histidine-rich region (HRR, amino acids 60 to 116)\r\ndid not affect knob density or shape, and lipid-binding assays confirmed no interaction between HRR\r\nand common iRBC lipids, even in the presence of Zn²⁺. Although largely unstructured, the β-sheet core\r\nof KAHRP is crucial for knob formation and structural integrity.\r\nTo investigate protein export, I employed stevor-miniTurbo biotin ligase fusion proteins with wild-type\r\nor altered PEXEL motifs to arrest export at distinct stages: ER (RLWAQ construct stevor1-8050W), PV\r\n(RLLEQ construct stevor1-8051E), or allow normal export (RLLAQ). These constructs identified\r\nproteins interacting with the PEXEL motif or PEXEL-exported proteins, elucidating the molecular\r\nmachinery of the export pathway. Mass spectrometry revealed several novel, potential interaction\r\npartners, and Split-GFP assay confirmed the interaction with SEC12, a guanine nucleotide exchange\r\nfactor (PF3D7_1116400) involved in COPII vesicle transport, suggesting protein trafficking via\r\nvesicular transport from ER to Golgi complex – a poorly studied organelle in Plasmodium. Another\r\nconfirmed interaction partner, a liver-stage antigen 3 (LSA-3, PF3D7_0220000), conferred its\r\nlocalization and function in the PV.\r\nThis data emphasizes the importance of the Golgi complex as a potential site for post-translational\r\nmodifications of PEXEL proteins. It further underscores the need to investigate the functional\r\ncontributions of LSA-3, which has primarily been studied in immune contexts, to export machinery.\r\nThis study also reveals the importance of β-sheet structured region of KAHRP in knob assembly. These\r\nfindings provide a foundation for understanding the molecular details of protein export and\r\ncytoadhesion, to open avenues for creating therapeutic interventions that disrupt Plasmodium\r\nfalciparum virulence."^^ . "2025" . . . . . . . "Violeta"^^ . "Pancakova"^^ . "Violeta Pancakova"^^ . . . . . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components (PDF)"^^ . . . "Violeta Pancakova Thesis 2025 PDF-A.pdf"^^ . . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components (Other)"^^ . . . . . . "small.jpg"^^ . . . "Protein export and cytoadhesion in Plasmodium\r\nfalciparum: structure-functional analysis of\r\nKAHRP and proteomic discovery of novel\r\nexport pathway components (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #36908 \n\nProtein export and cytoadhesion in Plasmodium \nfalciparum: structure-functional analysis of \nKAHRP and proteomic discovery of novel \nexport pathway components\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .