2LKL

Structure of the core intracellular domain of PfEMP1

Summary for 2LKL

• Entry DOI: 10.2210/pdb2lkl/pdb
• NMR Information: BMRB: 16911
• Descriptor: Erythrocyte membrane protein 1 (PfEMP1) (1 entity in total)
• Functional Keywords: helical protein, cell adhesion
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 1
• Total formula weight: 9722.96

Authors

Vakonakis, I.,Erat, M.C. (deposition date: 2011-10-16, release date: 2012-01-25, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

SOLUTION NMR