6S8U
Structure of the PfEMP1 IT4var13 DBLbeta domain bound to ICAM-1
Summary for 6S8U
| Entry DOI | 10.2210/pdb6s8u/pdb |
| Descriptor | Erythrocyte membrane protein 1, Intercellular adhesion molecule 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | pfemp1, malaria, cytoadhesion, icam-1, cell adhesion |
| Biological source | Plasmodium falciparum More |
| Total number of polymer chains | 2 |
| Total formula weight | 75201.44 |
| Authors | Lennartz, F.,Higgins, M.K. (deposition date: 2019-07-10, release date: 2019-09-25, Last modification date: 2024-11-13) |
| Primary citation | Lennartz, F.,Smith, C.,Craig, A.G.,Higgins, M.K. Structural insights into diverse modes of ICAM-1 binding byPlasmodium falciparum-infected erythrocytes. Proc.Natl.Acad.Sci.USA, 116:20124-20134, 2019 Cited by PubMed Abstract: A major determinant of pathogenicity in malaria caused by is the adhesion of parasite-infected erythrocytes to the vasculature or tissues of infected individuals. This occludes blood flow, leads to inflammation, and increases parasitemia by reducing spleen-mediated clearance of the parasite. This adhesion is mediated by PfEMP1, a multivariant family of around 60 proteins per parasite genome which interact with specific host receptors. One of the most common of these receptors is intracellular adhesion molecule-1 (ICAM-1), which is bound by 2 distinct groups of PfEMP1, A-type and B or C (BC)-type. Here, we present the structure of a domain from a B-type PfEMP1 bound to ICAM-1, revealing a complex binding site. Comparison with the existing structure of an A-type PfEMP1 bound to ICAM-1 shows that the 2 complexes share a globally similar architecture. However, while the A-type PfEMP1 bind ICAM-1 through a highly conserved binding surface, the BC-type PfEMP1 use a binding site that is more diverse in sequence, similar to how PfEMP1 interact with other human receptors. We also show that A- and BC-type PfEMP1 present ICAM-1 at different angles, perhaps influencing the ability of neighboring PfEMP1 domains to bind additional receptors. This illustrates the deep diversity of the PfEMP1 and demonstrates how variations in a single domain architecture can modulate binding to a specific ligand to control function and facilitate immune evasion. PubMed: 31527263DOI: 10.1073/pnas.1911900116 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.67 Å) |
Structure validation
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