My personal and professional adventure into Science

Our Severe Childhood Malaria paper is out in Cell Host & Microbe

Merry Christmas Everyone !
I just got an early Christmas present as I didn’t notice before now, that our Malaria paper was actually published in Cell Host & Microbe on the 4th December. I am actually a little surprised that no email was sent to me from the journal…

Anyways, I am very happy to be involved in such important research so I hope you will enjoy reading the paper as much as I will šŸ™‚

You can download the paper here:Ā Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria.

 


 

Clinton K.Y. Lau, Louise Turner, Jakob S. Jespersen, Edward D. Lowe, Bent Petersen, Christian W. Wang, Jens E.V. Petersen, John Lusingu, Thor G. Theander, Thomas Lavstsen, Matthew K. Higgins

Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria,

Cell Host & Microbe, Available online 4 December 2014, ISSN 1931-3128, http://dx.doi.org/10.1016/j.chom.2014.11.007. (http://www.sciencedirect.com/science/article/pii/S1931312814004235)

Abstract

The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRĪ±1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRĪ±1:EPCR complexes with analysis of 885 CIDRĪ±1 sequences, showing that the EPCR-binding surfaces of CIDRĪ±1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRĪ±1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding.

 

Diversity and Conservation in the CIDRĪ±1 Domains (A) The 14 completely conserved residues in CIDRĪ±1 domains, shown as red sticks on the HB3var03 CIDRĪ±1 structure. Residues with a property entropy score of less than 0.2 (but not totally conserved) are orange, and those with scores of 0.2ā€“0.3 are yellow. The inset shows a surface representation in the same orientation and colors, showing that conserved residues cluster in the domain center. (B) A sequence logo showing variation in CIDRĪ±1 residues that directly contact EPCR. (C and D) Structure of the EPCR-binding surface of the HB3var03 CIDRĪ±1 domain. Residues shown as sticks make direct interactions with EPCR.

 

 

 

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