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

被引:223
作者
Smith, JD
Subramanian, G
Gamain, B
Baruch, DI
Miller, LH
机构
[1] Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA
[2] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
关键词
malaria; antigenic variation; Plasmodium;
D O I
10.1016/S0166-6851(00)00279-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 between infected erythrocytes and host cells and is expressed in a clonally variant pattern at the erythrocyte surface. We describe by sequence analysis the 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 (DBL) domains. Previous work has shown that CIDR and DBL domains can possess adhesive properties. CIDR domains grouped as three distinct sequence classes (alpha, beta, and gamma) and DBL domains as five sequence classes (alpha, beta, gamma, delta. and epsilon). Consensus motifs are described for the different DBL and CIDR types. Whereas the number of DBL and CIDR domains vary between PfEMP1, PfEMP1 domain architecture is not random in that certain tandem domain associations - such as DBL alpha CIDR alpha, DBL beta CIDR beta, and DBL beta C2 - are preferentially observed. This conservation may have functional significance for PfEMP1 folding, transport, or binding activity. Parasite binding phenotype appears to be a determinant of infected erythrocyte 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 binding property. This information might be used to develop interventions targeting parasite binding variants that cause disease. (C) 2000 Elsevier science B.V. All rights reserved.
引用
收藏
页码:293 / 310
页数:18
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