@article{0c40e41377a241e1b1d66b0472dcbea9,
title = "Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A",
abstract = "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.",
author = "Kavita Singh and Gittis, {Apostolos G.} and Phuc Nguyen and Gowda, {D. Channe} and Miller, {Louis H.} and Garboczi, {David N.}",
note = "Funding Information: We thank A. Diouf and C.A. Long (Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases) for screening monoclonal antibodies, J.F. Andersen for helping with ITC, S. Madala for giving assistance with flow cytometry, H.-P. Su for advising on molecular biology, J.M. Moore for helping with initial protein purification and J.D. Smith (Seattle Biomedical Research Institute) for giving us the A4 genomic DNA. X-ray data were collected at the SBC-CAT and SER-CAT beamlines at the Advanced Photon Source supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract W-31-109-Eng-38. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Allergy and Infectious Diseases and by grant AI45086 for work performed in the laboratory of D.C. Gowda.",
year = "2008",
month = sep,
doi = "10.1038/nsmb.1479",
language = "English (US)",
volume = "15",
pages = "932--938",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Research",
number = "9",
}