5MZA

The DBLb domain of PF11_0521 PfEMP1 bound to human ICAM-1

5MZA の概要

• エントリーDOI: 10.2210/pdb5mza/pdb
• 分子名称: 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)
• 機能のキーワード: pfemp1 icam-1 cerebral malaria, cell adhesion
• 由来する生物種: Plasmodium falciparum 3D7; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77797.55

構造登録者

Lennartz, F.,Higgins, M.K. (登録日: 2017-01-31, 公開日: 2017-03-22, 最終更新日: 2024-10-16)

主引用文献

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

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: 28279348
DOI: 10.1016/j.chom.2017.02.009

実験手法

X-RAY DIFFRACTION (2.78 Å)