The structural basis for CD36 binding by the malaria parasite

Fu-Lien Hsieh; Louise Turner; Jani Reddy Bolla; Carol V Robinson; Thomas Lavstsen; Matthew K Higgins

doi:10.1038/ncomms12837

The structural basis for CD36 binding by the malaria parasite

Fu-Lien Hsieh, Louise Turner, Jani Reddy Bolla, Carol V Robinson, Thomas Lavstsen, Matthew K Higgins

81 Citations (Scopus)

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Abstract

CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum, tethering parasite-infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1 proteins maintain the ability to tether to the endothelium and avoid splenic clearance.

Original language	English
Article number	12837
Journal	Nature Communications
Volume	7
Number of pages	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms12837
Publication status	Published - 26 Sept 2016

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title = "The structural basis for CD36 binding by the malaria parasite",

abstract = "CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum, tethering parasite-infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1 proteins maintain the ability to tether to the endothelium and avoid splenic clearance.",

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T1 - The structural basis for CD36 binding by the malaria parasite

AU - Hsieh, Fu-Lien

AU - Turner, Louise

AU - Bolla, Jani Reddy

AU - Robinson, Carol V

AU - Lavstsen, Thomas

AU - Higgins, Matthew K

PY - 2016/9/26

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AB - CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum, tethering parasite-infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1 proteins maintain the ability to tether to the endothelium and avoid splenic clearance.

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The structural basis for CD36 binding by the malaria parasite

Abstract

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