Classification of adhesive domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 family

The Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family of cytoadherent proteins has a central role in disease from malaria infection . This highly diverse gene family is involved in binding interactions betwe en infected erythrocytes and host cells and is expressed in a clonally vari ant pattern at the erythrocyte surface. We describe by sequence analysis th e structure and domain organization of 20 PfEMP1 from the GenBank database. Four domains comprise the majority of PfEMP1 extracellular sequence: the N -terminal segment (NTS) located at the amino terminus of all PfEMP1, the C2 , the Cysteine-rich Interdomain Region (CIDR) and the Duffy Binding-like (D BL) domains. Previous work has shown that CIDR and DBL domains can possess adhesive properties. CIDR domains grouped as three distinct sequence classe s (alpha, beta, and gamma) and DBL domains as five sequence classes (alpha, beta, gamma, delta. and epsilon). Consensus motifs are described for the d ifferent DBL and CIDR types. Whereas the number of DBL and CIDR domains var y between PfEMP1, PfEMP1 domain architecture is not random in that certain tandem domain associations - such as DBL alpha CIDR alpha, DBL beta CIDR be ta, and DBL beta C2 - are preferentially observed. This conservation may ha ve functional significance for PfEMP1 folding, transport, or binding activi ty. Parasite binding phenotype appears to be a determinant of infected eryt hrocyte tissue tropism that contributes to parasite survival, transmission, and disease outcome. The sequence classification of DBL and CIDR types may have predictive value for identifying PfEMP1 domains with a particular bin ding property. This information might be used to develop interventions targ eting parasite binding variants that cause disease. (C) 2000 Elsevier scien ce B.V. All rights reserved.