Mapping binding residues in the <i>Plasmodium vivax</i> domain that binds Duffy antigen during red cell invasion

Hans, Dhiraj; Pattnaik, Priyabrata; Bhattacharyya, Arindam; Shakri, Ahmad Rushdi; Yazdani, Syed Shams; Sharma, Monal; Choe, Hyeryun; Farzan, Michael; Chitnis, Chetan E.

doi:10.1111/j.1365-2958.2005.04484.x

Cited by 103 publications

(113 citation statements)

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“…Although polymorphic residues were widely distributed throughout the PvDBPII sequence, polymorphisms at residues 417, 437, and 503, either in single or in combination, can affect the efficacy of inhibitory antibodies against erythrocyte binding [23,35]. As these residues compose an important discontinuous epitope in PvDBP, which might be the main target for inhibitory antibodies, these polymorphisms could be subject to immune pressure responsible for parasite escape from the host immune system.…”

Section: Discussionmentioning

confidence: 99%

“…It has been confirmed that this strong positive selection pressure in PvDBPII promotes greater diversity [14,30]. The immune pressure drives the generation of new PvDBP variants that are still able to bind erythrocytes but become resistant to inhibitory antibodies, suggesting that this DBP region is under positive pressure at critical residues and under negative pressure at the residues involved in receptor recognition [22,23,35]. A low prevalence of variant N417K (38.9%) was observed among Myanmar isolates, but more than 50% of W437R (61.1%) and I503K (77.8%) were identified.…”

Section: Discussionmentioning

confidence: 99%

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Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Kang

Moon

Kim

et al. 2012

Malar J

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BackgroundPlasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed.MethodsFifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs.ResultsThirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII.ConclusionsPvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Kang

Moon

Kim

et al. 2012

Malar J

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“…Analysis of site-directed mutagenesis data suggests that additional residues, other than those identified above, are involved in the DARC binding site or have a role in receptor recognition [11,12]. Mutations that completely abrogated P. vivax DBP binding to the DARC receptor map to multiple locations on the DBL structure outside of the proposed binding groove and a number of those residues cluster together on the outer surface of the DBL structure, including residues in unstructured exposed regions (e.g., PkDBPα DBL H59, S60).…”

Section: Proposed Darc Recognition Sitementioning

confidence: 98%

“…Based on previous mutational analysis [10][11][12], key residues for DARC recognition were identified as a cluster of nonpolar residues (Y94, L168, I175) grouped adjacent to basic residues (K96, K100, R103, K177) on the subdomain 2 surface to promote interaction with the sulfated Y41 of DARC, a critical element for receptor recognition identified in in vitro assays [13]. Major conformational changes to the P. knowlesi DBPα DBL structure are not predicted for DBL-DARC interaction, although this interaction is thought to bring the subdomain 3 loop into close contact with the host cell surface possibly to stabilize the ligand-receptor interaction or lead to a subsequent event in invasion.…”

Section: Proposed Darc Recognition Sitementioning

confidence: 99%

“…Major conformational changes to the P. knowlesi DBPα DBL structure are not predicted for DBL-DARC interaction, although this interaction is thought to bring the subdomain 3 loop into close contact with the host cell surface possibly to stabilize the ligand-receptor interaction or lead to a subsequent event in invasion. Unlike EBA175-GPA interaction, sugar side chains on the erythrocyte receptor have no apparent role in promoting the specificity of the DBP-DARC ligand-receptor interaction [9,14].Analysis of site-directed mutagenesis data suggests that additional residues, other than those identified above, are involved in the DARC binding site or have a role in receptor recognition [11,12]. Mutations that completely abrogated P. vivax DBP binding to the DARC receptor map to multiple locations on the DBL structure outside of the proposed binding groove and a number of those residues cluster together on the outer surface of the DBL structure, including residues in unstructured exposed regions (e.g., PkDBPα DBL H59, S60).…”

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confidence: 93%

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The crystal structure of P. knowlesi DBPα DBL domain and its implications for immune evasion

McHenry

Adams

2006

Trends in Biochemical Sciences

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Plasmodium vivax invasion of human erythrocytes requires that the ligand domain of the Duffybinding protein (DBP) recognize its cognate erythrocyte receptor, making DBP a potential target for therapy. The recently determined crystal structure of the orthologous DBP ligand domain of the closely related simian malaria parasite Plasmodium knowlesi provides insight into the molecular basis for receptor recognition and raises important questions about the mechanism of immune evasion employed by the malaria parasite. Plasmodium merozoite invasion is a multi-step processInvasion of erythrocytes by malaria parasites is a multi-step process involving discrete parasite ligands and host cell receptors [1]. Duffy binding protein (DBP), the first such ligand identified in micronemes of invasive malaria merozoites [2], is absolutely vital for the invasion process of Plasmodium vivax [3]. Cysteine-rich region II of the DBP comprises the prototypical Duffy binding like (DBL) ligand domain [4,5], which is also found in other erythrocyte binding proteins (EBA-175, BAEBL, JESEBL) and in cytoadherence proteins (PfEMP-1) [6]. Although the putative ligand domains of these paralogues have <30% sequence identity, these cysteine-rich regions share a core set of conserved residues (e.g., cysteines and aromatic amino acids) believed to be structurally and functionally important. DBL domains of both the human parasite P. vivax DBP and simian parasite P. knowlesi DBPα interact with the Duffy antigen receptor for chemokines (DARC) [7] on the erythrocyte surface, leading to formation of a tight junction necessary for invasion. The crystal structure of the P. knowlesi DBPα DBL domain recently reported by Singh et al provides exciting insights into the functional character of the P. vivax DBP [8]. Plasmodium knowlesi α DBL structureThe overall structure of the P. knowlesi DBPα DBL is similar to that of the F1 and F2 DBL domains of EBA-175 [9]. All twelve conserved cysteines of the P. knowlesi DBPα DBL domain are involved in intradomain disulfide bridges that delimit three DBL subdomains in the backbone, which forms a 'boomerang-shaped unit'. The pattern of disulfide bonding is identical between the P. knowlesi DBPα DBL and the F1 and F2 DBLs of P. falciparum EBA-175, although the F2 has an additional disulfide bridge. Subdomains 1, 2, and 3 have two, one and three disulfide bonds, respectively, and are comprised of twelve alpha helices (Fig. 1). Residues 15-52 form a random-coil stretch that makes up subdomain 1. The region between subdomains 1 and 2 (residues 53-63) is disordered and missing from the crystal structure, but is predicted to form a flexible linker. The 'β finger' motifs that facilitate Subdomain 2 (residues 64-180) and subdomain 3 (residues 186-307) each contain six alpha helices and are attached by a short linker segment. Subdomain 3 forms a large loop stabilized by three disulfide bridges with alpha helix 8 atop alpha helices 7 and 9; however, the functional role of the subdomain 3 structure is unclear. Proposed DARC Re...

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Host genetics

Williams

2016

Advances in Malaria Research

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Mapping binding residues in the Plasmodium vivax domain that binds Duffy antigen during red cell invasion

Abstract: Summary Plasmodium vivax depends on interaction with the

Cited by 103 publications

References 40 publications

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

The crystal structure of P. knowlesi DBPα DBL domain and its implications for immune evasion

Host genetics

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