Malaria Parasite Plasmodium falciparum Erythrocyte Binding Antigen 140

From Proteopedia

Introduction

In 2010, malaria caused over 650,000 deaths.^[1] While this disease is both preventable and curable, many of those that live in areas where the disease is endemic do not have access to such resources. Although there is a vaccine currently undergoing clinical trials, results are not expected until 2014.^[1] The most recent vaccine research has focused on understanding a group of proteins in the erythrocyte-binding ligand (EBL) family. These proteins, which are found in the Plasmodium species, facilitate entry into erythrocytes during malarial infection by creating tight junctions between the host erythrocytes and parasite membranes. ^[2] There are four family members: erythrocyte-binding antigen 175 (PfEBA-175), erythrocyte-binding ligand 1 (PfEBL-1), erythrocyte-binding antigen 140 (PfEBA-140), and erythrocyte-binding antigen 181 (PfEBA-181).^[2] PfEBA-140 binds glycophorin C on host erythrocytes.^[2] Understanding the mechanism by which PfEBA-140 recognizes and engages glycophorin C on erythrocytes may lead to the future development of a new malaria vaccine.

General Structure

spinqualitylabelsall models Structure of RII PfEBA-140 (PDB entry 4GF2) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The EBL family members, including PfEBA-140, are made up of two regions, region II (RII) (shown to the right) and region VI.[2] Region II is responsible for receptor binding in all EBL family members.[2] RII is composed of , F1 (purple) and F2 (teal).[2] These two DBL domains are connected by a .[2] The DBL protein fold is unique to the Plasmodium species. Not only does it have the ability to recognize and bind many erythrocyte cell receptors, but it also mediates microvasculature adherence of infected erythrocytes by erythrocyte membrane protein 1 (PfEMP1).[2] Each DBL domain is composed of three subdomains, illustrated in the pictures below. Subdomains of F1 and F2 In the above image, the subdomains S1, S2, and S3 of each of the F1 and F2 domains, as well as the helical linker, are illustrated.[2] Subdomains of F1 and F2 In the above image, structures of the individual subdomains are illustrated.[2] The colors are the same in both images: F1 subdomain 1 is shown in bronze, subdomain 2 in orange, subdomain 3 in dark orange; F2 subdomain 1 is shown in dark blue, subdomain 2 in blue, and subdomain 3 in light blue.

References

1. ↑ ^{1.0 1.1} http://www.who.int/mediacentre/factsheets/fs094/en/index.html
2. ↑ ^{2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9} Lin DH, Malpede BM, Batchelor JD, Tolia NH. Crystal and Solution Structures of Plasmodium falciparum Erythrocyte-binding Antigen 140 Reveal Determinants of Receptor Specificity during Erythrocyte Invasion. J Biol Chem. 2012 Oct 26;287(44):36830-6. doi: 10.1074/jbc.M112.409276. Epub 2012, Sep 18. PMID:22989878 doi:10.1074/jbc.M112.409276