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Engagement rules that underpin DBL-DARC interactions for ingress of Plasmodium knowlesi and Plasmodium vivax into human erythrocytes

Manickam Yogavel, Abhishek Jamwal, Swati Gupta, Amit Sharma
doi: https://doi.org/10.1101/147769
Manickam Yogavel
1Molecular Medicine Group International Center for Genetic Engineering and Biotechnology, New Delhi, India
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Abhishek Jamwal
1Molecular Medicine Group International Center for Genetic Engineering and Biotechnology, New Delhi, India
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Swati Gupta
1Molecular Medicine Group International Center for Genetic Engineering and Biotechnology, New Delhi, India
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Amit Sharma
1Molecular Medicine Group International Center for Genetic Engineering and Biotechnology, New Delhi, India
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Summary

The molecular mechanisms by which P. knowlesi and P. vivax invade human red blood cells have long been studied. Malaria parasite erythrocytic stages comprise of repeated bursts of parasites via cyclical invasion of host RBCs using dedicated receptor-ligand interactions. A family of erythrocyte-binding proteins (EBPs) from P. knowlesi and P. vivax attach to human Duffy antigen receptor for chemokines (DARC) via their Duffy binding-like domains (Pv-DBL and Pk-DBL respectively) for invasion. Here, we provide a comprehensive overview that presents new insights on the atomic resolution interactions that underpin the binding of human DARC with Pk/Pv-DBLs. Based on extensive structural and biochemical data, we provide a novel, testable and overarching interaction model that rationalizes even contradictory pieces of evidence that have so far existed in the literature on Pk/Pv-DBL/DARC binding determinants. We address the conundrum of how parasite-encoded Pk/Pv-DBLs recognize human DARC via its two sulfated tyrosine residues. We collate evidence for two distinct DARC integration sites on Pk/Pv-DBLs that together likely engage the DARC’s sulfated extracellular domain. These analyses are important for both malaria vaccine and inhibitor development efforts that are targeted at abrogating Pk/Pv-DBL/DARC coupling as one avenue to prevent invasion of P. vivax into human red blood cells.

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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 December 13, 2017.
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Engagement rules that underpin DBL-DARC interactions for ingress of Plasmodium knowlesi and Plasmodium vivax into human erythrocytes
Manickam Yogavel, Abhishek Jamwal, Swati Gupta, Amit Sharma
bioRxiv 147769; doi: https://doi.org/10.1101/147769
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Engagement rules that underpin DBL-DARC interactions for ingress of Plasmodium knowlesi and Plasmodium vivax into human erythrocytes
Manickam Yogavel, Abhishek Jamwal, Swati Gupta, Amit Sharma
bioRxiv 147769; doi: https://doi.org/10.1101/147769

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