RT Journal Article
SR Electronic
T1 Engagement rules that underpin DBL-DARC interactions for ingress of <em>Plasmodium knowlesi</em> and <em>Plasmodium vivax</em> into human erythrocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 147769
DO 10.1101/147769
A1 Yogavel, Manickam
A1 Jamwal, Abhishek
A1 Gupta, Swati
A1 Sharma, Amit
YR 2017
UL http://biorxiv.org/content/early/2017/12/13/147769.abstract
AB 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.