Reticulocyte binding protein homologs (RHs) are a superfamily of proteins found in Plasmodium responsible for cell invasion. Together with the family of erythrocyte binding-like proteins (EBLs) they make up the two families of invasion proteins universal to Plasmodium.[1] The two families function cooperatively.[2]
This family is named after the reticulocyte binding proteins in P. vivax, a parasite that only infects reticulocytes (immature red blood cells) expressing the Duffy antigen. Homologs have since been identified in P. yoelii and P. reichenowi.[1]
A P. falciparumprotein complex called PfRH5-PfCyRPA-PfRipr (RCR) is known to bind basigin via the tip of RH5.[3] The trimeric complex forms an elongated structure with RH5 and Ripr on distal ends and CyRPA in the middle.[4] The RCR complex has been identified as a promising malaria vaccine target with each individual component capable of inducing strain transcending immunity in in vitro assays of parasite growth.[5] Of the entire family of RHs, only RH5 appears to be essential for invasion and functions downstream of the other RHs during invasion.[6]
RHs do not express any significant sequence feature for specific domains, except for a set of transmembrane helices at the C-terminal. From experimentation on partial proteins, RHs are known to contain enterocyte-binding and nucleotide-sensing domains (EBD and NBD) that may partially overlap. The structure of the EBD has been experimentally observed in 2011 by small angle X-ray scattering.[8] A much better crystal structure for an N-terminal receptor-binding domain (presumably the same as EBD) was published in 2014.[3]
