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Combining IP3 affinity chromatography and bioinformatics reveals a novel protein-IP3 binding site on Plasmodium falciparum MDR1 transporter

Eduardo Alves, Helder Nakaya, Euzébio Guimarães, View ORCID ProfileCélia R. S. Garcia
doi: https://doi.org/10.1101/2021.03.25.437059
Eduardo Alves
1Life Science Department, Imperial College London, London, UK
2Department of Clinical and Toxicological Analyses of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
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Helder Nakaya
2Department of Clinical and Toxicological Analyses of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
3Computational Systems Biology Laboratory, INOVA, University of Sao Paulo, Sao Paulo, Brazil
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Euzébio Guimarães
4Federal University of Rio Grande do Norte, Pharmacy Department, Health Science Center, Natal, Brazil
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Célia R. S. Garcia
2Department of Clinical and Toxicological Analyses of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
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  • ORCID record for Célia R. S. Garcia
  • For correspondence: cgarcia@usp.br
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Abstract

Intracellular Ca2+ mobilization induced by second messenger IP3 controls many cellular events in most of the eukaryotic groups. Despite the increasing evidence of IP3-induced Ca2+ in apicomplexan parasites like Plasmodium, responsible for malaria infection, no protein with potential function as an IP3-receptor has been identified. The use of bioinformatic analyses based on previously known sequences of IP3-receptor failed to identify potential IP3-receptor candidates in any Apicomplexa. In this work, we combine the biochemical approach of an IP3 affinity chromatography column with bioinformatic meta-analyses to identified potential vital membrane proteins that present binding with IP3 in Plasmodium falciparum. Our analyses reveal that PF3D7_0523000, a gene that codes a transport protein associated with multidrug resistance, as a potential target for IP3. This work provides a new insight for probing potential candidates for IP3-receptor in Apicomplexa.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 25, 2021.
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Combining IP3 affinity chromatography and bioinformatics reveals a novel protein-IP3 binding site on Plasmodium falciparum MDR1 transporter
Eduardo Alves, Helder Nakaya, Euzébio Guimarães, Célia R. S. Garcia
bioRxiv 2021.03.25.437059; doi: https://doi.org/10.1101/2021.03.25.437059
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Combining IP3 affinity chromatography and bioinformatics reveals a novel protein-IP3 binding site on Plasmodium falciparum MDR1 transporter
Eduardo Alves, Helder Nakaya, Euzébio Guimarães, Célia R. S. Garcia
bioRxiv 2021.03.25.437059; doi: https://doi.org/10.1101/2021.03.25.437059

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