Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A

被引：81
作者：
Singh, Kavita [1 ]
Gittis, Apostolos G. [1 ]
Nguyen, Phuc [1 ]
Gowda, D. Channe [2 ]
Miller, Louis H. [3 ]
Garboczi, David N. [1 ]
机构：
[1] NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA
[2] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA
[3] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA
来源：
NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2008年 / 15卷 / 09期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1038/nsmb.1479
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：
Plasmodium falciparum-infected erythrocytes bind to chondroitin sulfate A (CSA) in the placenta via the VAR2CSA protein, a member of the P. falciparum erythrocyte membrane protein-1 family, leading to life-threatening malaria in pregnant women with severe effects on their fetuses and newborns. Here we describe the structure of the CSA binding DBL3x domain, a Duffy binding-like (DBL) domain of VAR2CSA. By forming a complex of DBL3x with CSA oligosaccharides and determining its structure, we have identified the CSA binding site to be a cluster of conserved positively charged residues on subdomain 2 and subdomain 3. Mutation or chemical modification of lysine residues at the site markedly diminished CSA binding to DBL3x. The location of the CSA binding site is an important step forward in the molecular understanding of pregnancy-associated malaria and offers a new target for vaccine development.
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收藏
页码：932 / 938
页数：7
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