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 Citationer (Scopus)

103 Downloads (Pure)

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.

Originalsprog	Engelsk
Artikelnummer	12837
Tidsskrift	Nature Communications
Vol/bind	7
Antal sider	11
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms12837
Status	Udgivet - 26 sep. 2016

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1038/ncomms12837Licens: CC BY

ncomms12837Forlagets udgivne version, 2,27 MBLicens: CC BY

Citationsformater

@article{d8ff633a6a9b4a3686028a21f361b8be,

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.",

author = "Fu-Lien Hsieh and Louise Turner and Bolla, {Jani Reddy} and Robinson, {Carol V} and Thomas Lavstsen and Higgins, {Matthew K}",

year = "2016",

month = sep,

day = "26",

doi = "10.1038/ncomms12837",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

}

TY - JOUR

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

Y1 - 2016/9/26

N2 - 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.

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.

U2 - 10.1038/ncomms12837

DO - 10.1038/ncomms12837

M3 - Journal article

C2 - 27667267

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12837

ER -

The structural basis for CD36 binding by the malaria parasite

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater