Part:BBa_K3582001

The CIDRa domain from MCvar1 PfEMP1

Plasmodium species of parasite uses a set of adhesive proteins, called the PfEMP1, which are expressed on the surfaces of infected red blood cells, causing them to bind to blood vessels and tissues. The PfEMP1 are among the few parasite proteins constantly exposed to the host immune system during the blood phase of the parasite life cycle. Due to increasing selective pressure, this group of proteins have expanded into a complex protein family, with around 60 members in each parasite genome and a system of antigenic variation that allows parasites to switch which PfEMP1 they expose to the immune system. Antibodies that bind PfEMP1 are found in people from malaria-endemic regions and correlate with immunity from severe disease. For the facilitation of endothelial binding, PfEMP1 proteins contain huge extracellular ectodomains consisting of 2–10 copies of two domain types, the Duffy-binding like (DBL) and cysteine-rich interdomain region (CIDR) domains. Interestingly, it is found that these domains are extremely variable in sequence, yet they share a conserved architecture and can be classified into different subgroups based on the sequence.The CIDRa2 domains have a hydrophobic pocket that binds to a protruding phenylalanine residue from CD36. This biobrick allows us to synthesize the CIDRa Domain of MC variant of PfEMP1 protein to study the interaction. A strep II tag is inserted in the end for ease of purification.

Figure 1.A zoomed view of the binding interfaces that mediate the CIDRa2: CD36 interaction.(PDB:5LGD-Fu-Lien Hsieh1 et al.)

Figure 2.Structure of the CIDRa domain from MCvar1 PfEMP1 visualized using Chimera

Figure 1. Structure of CD36(Red) interacting with CIDRa domain of MCvar1 PfEMP1 protein(Blue).

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

References

• The structural basis for CD36 binding by the malaria parasite.

Fu-Lien Hsieh1, Louise Turner2, Jani Reddy Bolla3, Carol V. Robinson3, Thomas Lavstsen2 & Matthew K. Higgins1

• Gardner, M. J. et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511 (2002).
• Chan, J. A. et al. Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity. J. Clin. Invest. 122, 3227–3238 (2012).