Receptor-binding residues lie in central regions of Duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites
Receptor-binding residues lie in central regions of Duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites
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DOI：
10.1182/blood-2004-05-1722
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发表时间：
2005-03-15
期刊：
影响因子：
20.3
通讯作者：
Chitnis, CE
中科院分区：
文献类型：
--
作者：
Mayor, A;Bir, N;Chitnis, CE
疟原虫侵入红细胞和恶性疟原虫感染红细胞粘附于宿主毛细血管是疟疾的两种主要致病机制。红细胞结合蛋白（EBP）的受体结合结构域，如恶性疟原虫EBA-175，它介导的入侵，和恶性疟原虫红细胞膜蛋白1（PfEMP-1）家族成员，这是由var基因编码和介导的细胞粘附，已被定位到保守的富含半胱氨酸的结构域称为达菲结合样（DBL）结构域。在这里，我们已经映射区域内DBL域从EBP和PfEMP-1含有受体结合残基。使用生物化学和分子生物学方法，我们证明了寄生虫配体的受体结合残基结合唾液酸血型糖蛋白A的入侵以及补体受体-1和硫酸软骨素A的细胞粘附地图DBL域的中心区域。相反，与细胞间粘附分子1（ICAM-1）的结合需要DBL β C2结构域的中心和末端区域。确定DBL结构域内的功能区域是理解其与不同宿主受体相互作用的结构-功能基础的第一步。(c)2005年美国血液学会
Erythrocyte invasion by malaria parasites and cytoadherence of Plasmodium falciparum-infected erythrocytes to host capillaries are 2 key pathogenic mechanisms in malarid. The receptor-binding domains of erythrocyte-binding proteins (EBPs) such as Plasmodium falciparum EBA-175, Which mediate invasion, and P falciparum erythrocyte Membrane protein 1 (PfEMP-1) family members, which are encoded by var genes and mediate cytoadherence, have been mapped to conserved cysteine-rich domains referred to as Duffy-binding-like (DBL) domains. Here, we,have mapped regions within DBL domains from EBPs and PfEMP-1 that contain receptor-binding residues. Using biochemical and molecular methods we demonstrate that the receptor-binding residues of parasite ligands that bind sialic acid on glycophorin A for invasion as well as complement receptor-1 and chondroitin sulfate A for cytoadherence map to central regions of DBL domains. In contrast, binding to intercellular adhesion molecule 1 (ICAM-1) requires both the central and terminal regions of DBL beta C2 domains. Determination of functional regions within DBL domains is the first step toward understanding the structure-function bases for their interaction with diverse host receptors. (c) 2005 by The American Society of Hematology