2LKL

Structure of the core intracellular domain of PfEMP1

2LKL の概要

• エントリーDOI: 10.2210/pdb2lkl/pdb
• NMR情報: BMRB: 16911
• 分子名称: Erythrocyte membrane protein 1 (PfEMP1) (1 entity in total)
• 機能のキーワード: helical protein, cell adhesion
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9722.96

構造登録者

Vakonakis, I.,Erat, M.C. (登録日: 2011-10-16, 公開日: 2012-01-25, 最終更新日: 2024-05-15)

主引用文献

Mayer, C.,Slater, L.,Erat, M.C.,Konrat, R.,Vakonakis, I.
Structural Analysis of the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) Intracellular Domain Reveals a Conserved Interaction Epitope.
J.Biol.Chem., 287:7182-7189, 2012

PubMed Abstract: Plasmodium falciparum-infected red blood cells adhere to endothelial cells, thereby obstructing the microvasculature. Erythrocyte adherence is directly associated with severe malaria and increased disease lethality, and it is mediated by the PfEMP1 family. PfEMP1 clustering in knob-like protrusions on the erythrocyte membrane is critical for cytoadherence, however the molecular mechanisms behind this system remain elusive. Here, we show that the intracellular domains of the PfEMP1 family (ATS) share a unique molecular architecture, which comprises a minimal folded core and extensive flexible elements. A conserved flexible segment at the ATS center is minimally restrained by the folded core. Yeast-two-hybrid data and a novel sequence analysis method suggest that this central segment contains a conserved protein interaction epitope. Interestingly, ATS in solution fails to bind the parasite knob-associated histidine-rich protein (KAHRP), an essential cytoadherence component. Instead, we demonstrate that ATS associates with PFI1780w, a member of the Plasmodium helical interspersed sub-telomeric (PHIST) family. PHIST domains are widespread in exported parasite proteins, however this is the first specific molecular function assigned to any variant of this family. We propose that PHIST domains facilitate protein interactions, and that the conserved ATS epitope may be targeted to disrupt the parasite cytoadherence system.

PubMed: 22249178
DOI: 10.1074/jbc.M111.330779

実験手法

SOLUTION NMR