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Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1.

Brown, Alan, Turner, Louise, Christoffersen, Stig, Andrews, Katrina A, Szestak, Tadge, Zhao, Yuguang, Larsen, Sine, Craig, Alister ORCID: and Higgins, Matthew K (2013) 'Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1.'. The Journal of Biological Chemistry, Vol 288, Issue 8, pp. 5992-6003.

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The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria. The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from CIDR (cysteine-rich interdomain regions) and DBL (Duffy-binding-like) domains and show extensive variation in sequence, size, and domain organization. Here we use biophysical methods to characterize the entire ∼300-kDa ectodomain from IT4VAR13, a protein that interacts with the host receptor, intercellular adhesion molecule-1 (ICAM-1). We show through small angle x-ray scattering that IT4VAR13 is rigid, elongated, and monomeric. We also show that it interacts with ICAM-1 through the DBLβ domain alone, forming a 1:1 complex. These studies provide a first low resolution structural view of a PfEMP1 ectodomain in complex with its ligand. They show that it combines a modular domain arrangement consisting of individual ligand binding domains, with a defined higher order architecture that exposes the ICAM-1 binding surface to allow adhesion.

Item Type: Article
Subjects: QU Biochemistry > Cells and Genetics > QU 375 Cell physiology
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 150 Erythrocytes
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):
Depositing User: Mary Creegan
Date Deposited: 18 Jun 2013 15:34
Last Modified: 17 Jul 2019 14:14


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