| Structural highlights
Function
[ICAM1_HUMAN] ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. In case of rhinovirus infection acts as a cellular receptor for the virus.[1] [2] [3] [4]
Publication Abstract from PubMed
Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria.
Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria.,Lennartz F, Adams Y, Bengtsson A, Olsen RW, Turner L, Ndam NT, Ecklu-Mensah G, Moussiliou A, Ofori MF, Gamain B, Lusingu JP, Petersen JE, Wang CW, Nunes-Silva S, Jespersen JS, Lau CK, Theander TG, Lavstsen T, Hviid L, Higgins MK, Jensen AT Cell Host Microbe. 2017 Mar 8;21(3):403-414. doi: 10.1016/j.chom.2017.02.009. PMID:28279348[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, Kamarck ME, McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839-47. PMID:2538243
- ↑ Marlin SD, Staunton DE, Springer TA, Stratowa C, Sommergruber W, Merluzzi VJ. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature. 1990 Mar 1;344(6261):70-2. PMID:1968231 doi:http://dx.doi.org/10.1038/344070a0
- ↑ Hayashi T, Takahashi T, Motoya S, Ishida T, Itoh F, Adachi M, Hinoda Y, Imai K. MUC1 mucin core protein binds to the domain 1 of ICAM-1. Digestion. 2001;63 Suppl 1:87-92. PMID:11173916
- ↑ van Buul JD, Allingham MJ, Samson T, Meller J, Boulter E, Garcia-Mata R, Burridge K. RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration. J Cell Biol. 2007 Sep 24;178(7):1279-93. Epub 2007 Sep 17. PMID:17875742 doi:10.1083/jcb.200612053
- ↑ Lennartz F, Adams Y, Bengtsson A, Olsen RW, Turner L, Ndam NT, Ecklu-Mensah G, Moussiliou A, Ofori MF, Gamain B, Lusingu JP, Petersen JE, Wang CW, Nunes-Silva S, Jespersen JS, Lau CK, Theander TG, Lavstsen T, Hviid L, Higgins MK, Jensen AT. Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria. Cell Host Microbe. 2017 Mar 8;21(3):403-414. doi: 10.1016/j.chom.2017.02.009. PMID:28279348 doi:http://dx.doi.org/10.1016/j.chom.2017.02.009
|
