Taxonomic group: protista / Apicomplexa
(Phylum: Apicomplexa)
Host organism: Homo sapiens
Associated disease: malaria due to Plasmodium falciparum [ICD11:
1F40 
, ICD11:
XN69B ]
NCBI PubMed ID: 24090058Publication DOI: 10.1111/febs.12541Journal NLM ID: 101229646Publisher: Blackwell Publishing
Correspondence: sangdunchoi
ajou.ac.kr
Institutions: Department of Molecular Science and Technology, Ajou University, Suwon, Korea
Proinflammatory responses by Toll-like receptors (TLRs) to malaria infection are considered to be a significant factor in suppressing pathogen growth and in disease control. The key protozoan parasite Plasmodium falciparum causes malaria through glycosylphosphatidylinositols (GPIs), which induce the host immune response mainly via TLR2 signalling. Experimental studies have suggested that malarial GPIs from P. falciparum are recognized by the TLR2 subfamily. However, the interaction site and their involvement in the activation mechanism are still unknown. A better understanding of the detailed structure of the TLR-GPI interaction is important for the design of more effective anti-malarial therapeutics. We used a molecular docking method to predict the binding regions of malarial GPIs with the TLR2 subfamily members. We also employed molecular dynamics simulations and principal component analysis to understand ligand-induced conformational changes of the TLR2 subfamily. We observed the expected structural changes upon ligand binding, and significant movements were found in loop regions located in the ligand-binding site of the TLR2 subfamily. We further propose that the binding modes of malarial GPIs are similar to lipopeptides, and that the lipid portions of the ligands could play an essential role in selective dimerization of the TLR2 subfamily.
Toll-like receptor, Glycosylphosphatidylinositol, molecular dynamics simulation, molecular docking, Plasmodium falciparum, principal component analysis
Structure type: oligomer
Location inside paper: Fig. 6, Fig. S1, Man4-GPI
Compound class: GPI-anchor
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130701,IEDB_136104,IEDB_140116,IEDB_141181,IEDB_141793,IEDB_141807,IEDB_141829,IEDB_141830,IEDB_141832,IEDB_143632,IEDB_144983,IEDB_151531,IEDB_152206,IEDB_153220,IEDB_187036,IEDB_474450,IEDB_534865,IEDB_76933,IEDB_983930,SB_136,SB_191,SB_196,SB_198,SB_44,SB_67,SB_72
Methods: MD simulations, PCA, molecular docking
Biological activity: The docked hTLR2-hTLR1–Man4-GPI complex showed a potential hydrogen bond between Gln316 of TLR1 and the GPI.
NCBI Taxonomy refs (TaxIDs): 5833
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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