Author
Brian Rojas
Bio: Brian Rojas is an academic researcher from Universidad de las Américas Puebla. The author has contributed to research in topics: Molecular mimicry & Plasmodium falciparum. The author has co-authored 1 publications.
Papers
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TL;DR: In this paper, a set of eight proteins with a remarkable resemblance to human proteins were found to be moonlighting proteins carried by Plasmodium falciparum molecules carried by extracellular vesicles.
Abstract: Red blood cells infected with Plasmodium falciparum secrete extracellular vesicles in order to facilitate the survival and infection of human cells. Various researchers have studied the composition of these extracellular vesicles and identified the proteins contained inside. In this work, we used that information to detect potential P. falciparum molecules that could be imitating host proteins. We carried out several searches to detect sequences and structural similarities between the parasite and host. Additionally, the possibility of functional mimicry was explored in line with the potential role that each candidate can perform for the parasite inside the host. Lastly, we determined a set of eight sequences (mainly moonlighting proteins) with a remarkable resemblance to human proteins. Due to the resemblance observed, this study proposes the possibility that certain P. falciparum molecules carried by extracellular vesicles could be imitating human proteins to manipulate the host cell's physiology.
3 citations
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TL;DR: In this paper , the authors show that Plasmodium falciparum (Pf)-infected red blood cells (RBCs) carry significantly higher sialylated complex N-glycans than those derived from healthy RBCs.
Abstract: Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells.
6 citations
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TL;DR: In this paper , the authors presented the first proteome-level search for tertiary structure similarity between proteins from Plasmodium falciparum, a malaria-causing parasite, and humans.
Abstract: Introduction Molecular mimicry is a strategy used by parasites to evade the host’s immune system and facilitate transmission to a new host. To date, high-throughput examples of molecular mimicry have been limited to comparing protein sequences. However, recent advances in the prediction of tertiary structural models, led by Deepmind’s AlphaFold, enable the comparison of thousands of proteins from parasites and their hosts at the structural level, allowing for the identification of more mimics. Here, we present the first proteome-level search for tertiary structure similarity between proteins from Plasmodium falciparum, a malaria-causing parasite, and humans. Methods We assembled a database of experimentally-characterized protein tertiary structures (from the Protein Data Bank) and AlphaFold-generated protein tertiary structures from P. falciparum, human, and 15 negative control species, i.e., species not infected by P. falciparum. We aligned human and control structures to the parasite structures using Foldseek. Results We identified molecular mimicry in three proteins that have been previously proposed as mediators of Plasmodium-human interactions. By extending this approach to all P. falciparum proteins, we identified an additional 41 potential mimics that are supported by additional experimental data. Discussion Our findings demonstrate a valuable application of AlphaFold-derived tertiary structural models, and we discuss key considerations for its effective use in other host-parasite systems.
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TL;DR: In this paper , the first proteome-level search for tertiary structure similarity between the proteins from Plasmodium falciparum and human was performed, and it was shown that seven evolved to molecularly mimic a human protein.
Abstract: Molecular mimicry is a strategy used by parasites to escape the host immune system and successfully transmit to a new host. To date, high-throughput examples of molecular mimicry have been limited to comparing protein sequences. However, with advances in the prediction of tertiary structural models, led by Deepmind’s AlphaFold, it is now possible to compare the tertiary structures of thousands of proteins from parasites and their hosts, to identify more subtle mimics. Here, we present the first proteome-level search for tertiary structure similarity between the proteins from Plasmodium falciparum and human. Of 206 P. falciparum proteins that have previously been proposed as mediators of Plasmodium-human interactions, we propose that seven evolved to molecularly mimic a human protein. By expanding the approach to all P. falciparum proteins, we identified a further 386 potential mimics, with 51 proteins corroborated by additional biological data. These findings demonstrate a valuable application of AlphaFold-derived tertiary structural models, and we discuss key considerations for its effective use in other host-parasite systems.