Engagement Rules That Underpin DBL-DARC Interactions for Ingress of and Into Human Erythrocytes.

Malaria parasite erythrocytic stages comprise of repeated bursts of parasites via cyclical invasion of host erythrocytes using dedicated receptor-ligand interactions. A family of erythrocyte-binding proteins from () and () attach to human Duffy antigen receptor for chemokines (DARC) via their Duffy binding-like domains (DBLs) for invasion. Here 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 /-DBL/DARC binding determinants. We further address the conundrum of how parasite-encoded /-DBLs recognize human DARC and collate evidence for two distinct DARC integration sites on /-DBLs.