5MZA
The DBLb domain of PF11_0521 PfEMP1 bound to human ICAM-1
Summary for 5MZA
| Entry DOI | 10.2210/pdb5mza/pdb |
| Descriptor | Erythrocyte membrane protein 1 (PfEMP1), Intercellular adhesion molecule 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | pfemp1 icam-1 cerebral malaria, cell adhesion |
| Biological source | Plasmodium falciparum 3D7 More |
| Total number of polymer chains | 2 |
| Total formula weight | 77797.55 |
| Authors | Lennartz, F.,Higgins, M.K. (deposition date: 2017-01-31, release date: 2017-03-22, Last modification date: 2024-10-16) |
| Primary citation | Lennartz, F.,Adams, Y.,Bengtsson, A.,Olsen, R.W.,Turner, L.,Ndam, N.T.,Ecklu-Mensah, G.,Moussiliou, A.,Ofori, M.F.,Gamain, B.,Lusingu, J.P.,Petersen, J.E.,Wang, C.W.,Nunes-Silva, S.,Jespersen, J.S.,Lau, C.K.,Theander, T.G.,Lavstsen, T.,Hviid, L.,Higgins, M.K.,Jensen, A.T. Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria. Cell Host Microbe, 21:403-414, 2017 Cited by PubMed Abstract: 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. PubMed: 28279348DOI: 10.1016/j.chom.2017.02.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.78 Å) |
Structure validation
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