恶性疟原虫-CD36 结构-功能关系的同源扫描诱变定义。
Plasmodium falciparum-CD36 Structure-Function Relationships Defined by Ortholog Scanning Mutagenesis.
机构信息
SAR Laboratories, Sandra Rotman Centre, Toronto General Hospital-University Health Network, Ontario, Canada.
Department of Cell Biology, Zhejiang University, School of Basic Medical Sciences, Hangzhou, People's Republic of China.
出版信息
J Infect Dis. 2019 Feb 23;219(6):945-954. doi: 10.1093/infdis/jiy607.
BACKGROUND
The interaction of Plasmodium falciparum-infected erythrocytes (IEs) with the host receptor CD36 is among the most studied host-parasite interfaces. CD36 is a scavenger receptor that binds numerous ligands including the cysteine-rich interdomain region (CIDR)α domains of the erythrocyte membrane protein 1 family (PfEMP1) expressed on the surface of IEs. CD36 is conserved across species, but orthologs display differential binding of IEs.
METHODS
In this study, we exploited these differences, combined with the recent crystal structure and 3-dimensional modeling of CD36, to investigate malaria-CD36 structure-function relationships and further define IE-CD36 binding interactions.
RESULTS
We show that a charged surface in the membrane-distal region of CD36 is necessary for IE binding. Moreover, IE interaction with this binding surface is influenced by additional CD36 domains, both proximal to and at a distance from this site.
CONCLUSIONS
Our data indicate that subtle sequence and spatial differences in these domains modify receptor conformation and regulate the ability of CD36 to selectively interact with its diverse ligands.
背景
恶性疟原虫感染的红细胞（IEs）与宿主受体 CD36 的相互作用是研究最多的宿主-寄生虫界面之一。CD36 是一种清道夫受体，可结合许多配体，包括表面表达的红细胞膜蛋白 1 家族（PfEMP1）的半胱氨酸丰富的结构域间区（CIDR）α 结构域。CD36 在物种间是保守的，但同源物显示出对 IEs 的不同结合。
方法
在这项研究中，我们利用这些差异，结合最近的 CD36 晶体结构和三维建模，研究疟疾-CD36 的结构-功能关系，并进一步定义 IE-CD36 结合相互作用。
结果
我们表明 CD36 膜远端区域的带电表面对于 IE 结合是必需的。此外，IE 与该结合表面的相互作用受该位点附近和远处的其他 CD36 结构域的影响。
结论
我们的数据表明，这些结构域中的微小序列和空间差异会改变受体构象，并调节 CD36 选择性与其各种配体相互作用的能力。
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