DARC shade of chemokine receptors

Chemokine Receptors (CR) are class-A G-protein coupled receptors (GPCR) and binds specifically to two major (CC, CXC) and minor classes (CX3C and XC) of chemokines. They are involved in inflammation, haemostasis, cancer metastasis pathways and many other regulatory mechanisms. Duffy Antigen / Chemokine Repector DARC) belongs to an atypical trend in the CR since it fails to transduce any signal as it lacks the famous DRY motif in the II intercellular loop of GPCR. Therefore, it is often ascribed to as a scavenger receptor and catalogued along the Atypical Chemokine Receptors (ACKR). Adding to this atypical behaviour, it binds to both major classes of CL. DARC also plays a major role in the host-entry mechanism of Plasmodium vivax (Pv), the second most endemic strain of malaria. The understanding of the structural dynamics of DARC - parasite interaction (through the Duffy Binding Protein) is of crucial importance in the battle against Plasmodium   v ivax . The literature on the DARC’s structure is highly scarce with only one structural model depicting the complete structure of monomeric DARC. However, the suggested mode of interaction for DARC is dimeric, as shown by Batchelor et al in 2014, J.Plos Pathogens. Therefore, we generated a highly robust structural model of dimeric DARC. The protocol for structural template selection is backed by the evolutionary relationships, conserved cysteines & TM regions and three different assessment scores (DOPE, HPM and MAIDEN). Moreover, the structural model is embedded in a lipid bilayer mimicking the real erythrocyte membrane composition. The steered molecular dynamics study of this model, while tracing the properties like, disulphide bonds, accessibility and local structural adaptation (using a specific structural alphabet; protein blocks) would provide crucial insights into the mechanism and may help us discover a drug-able target in DARC.