%0 Journal Article
%T Characterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood-Stage Antigen 332
%A Sandra Nilsson
%A Kirsten Moll
%A Davide Angeletti
%A Letusa Albrecht
%A Inari Kursula
%A Ning Jiang
%A Xiaodong Sun
%A Klavs Berzins
%A Mats Wahlgren
%A Qijun Chen
%J Malaria Research and Treatment
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/671439
%X Studies on Pf332, a major Plasmodium falciparum blood-stage antigen, have largely been hampered by the cross-reactive nature of antibodies generated against the molecule due to its high content of repeats, which are present in other malaria antigens. We previously reported the identification of a conserved domain in Pf332 with a high degree of similarity to the Duffy-binding-like (DBL) domains of the erythrocyte-binding-like (EBL) family. We here describe that antibodies towards Pf332-DBL are induced after repeated exposure to P. falciparum and that they are acquired early in life in areas of intense malaria transmission. Furthermore, a homology model of Pf332-DBL was found to be similar to the structure of the EBL-DBLs. Despite their similarities, antibodies towards Pf332-DBL did not display any cross-reactivity with EBL-proteins as demonstrated by immunofluorescence microscopy, Western blotting, and peptide microarray. Thus the DBL domain is an attractive region to use in further studies on the giant Pf332 molecule. 1. Introduction Plasmodium falciparum malaria is a major human disease that accounts for 1¨C2 million deaths annually [1]. The disease affects predominantly children under the age of five, as older children and adults living in malaria endemic areas become immune against severe forms of the disease after being repeatedly exposed to the parasite. During blood-stage development, P. falciparum parasites invade red blood cells (RBC) and cause them to sequester from the blood circulation by adhering to host endothelial cells. Both invasion and sequestration are central to the pathogenesis of malaria, and they require an adhesive cysteine-rich domain referred to as the Duffy-binding-like (DBL) domain. The DBL domains are present in two different protein families; the erythrocyte-binding-like (EBL) family of invasion proteins and the large and diverse P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of cytoadherence proteins [2, 3]. We recently reported the identification of a previously unknown domain in the P. falciparum antigen 332 with a high degree of similarity to the DBL domains of the EBL family [4]. Most EBL members are transmembrane proteins, which are expressed in schizonts and localize to merozoite micronemes from where they are released prior to or during host cell invasion [5]. In contrast, Pf332 is expressed in trophozoites and is later on cotransported together with the surface-destined PfEMP1 in parasite-induced membrane structures, referred to as MaurerĄ¯s clefts [6, 7]. In schizonts, Pf332 can be found in association
%U http://www.hindawi.com/journals/mrt/2011/671439/