title: Divergent binding sites on intercellular adhesion molecule-1 (ICAM-1) for variant Plasmodium falciparum isolates.
abstract: Adhesion of human erythrocytes infected with the malaria parasite Plasmodium falciparum to host endothelium has been associated with severe forms of this disease. A number of endothelial receptors have been identified, and there is evidence that one of these, intercellular adhesion molecule-1 (ICAM-1), may play an important role in the pathology of cerebral malaria. Mutagenesis of domain 1 of ICAM-1, which is involved in parasite adhesion, shows that the binding sites for different parasite variants overlap to a large extent, but that there are subtle differences between them that correlate with their adhesive phenotypes. This suggests that the ability to bind to ICAM-1 has arisen from a common variant, but that subsequent changes have led to differences in binding avidity, which may affect pathogenesis. The definition of common binding determinants and the elucidation of links between ICAM-1 binding phenotype and disease will provide new leads in the design of therapeutic interventions.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, UK.
authors.forename: Man Tsuey
authors.initials: MT
authors.lastname: Tse
authors.forename: Kausik
authors.initials: K
authors.lastname: Chakrabarti
authors.forename: Carolyn
authors.initials: C
authors.lastname: Gray
authors.forename: Chetan E
authors.initials: CE
authors.lastname: Chitnis
authors.forename: Alister
authors.initials: A
authors.lastname: Craig
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016779:Malaria, Cerebral / Q000469:parasitology; D008958:Models, Molecular; D016296:Mutagenesis; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D011485:Protein Binding
chemical_list: D018799:Intercellular Adhesion Molecule-1