The Experts below are selected from a list of 750 Experts worldwide ranked by ideXlab platform
Niraj H. Tolia - One of the best experts on this subject based on the ideXlab platform.
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Dimerization of Plasmodium vivax DBP is induced upon receptor Binding and drives recognition of DARC
Nature Structural & Molecular Biology, 2011Co-Authors: Joseph D. Batchelor, Jacob A. Zahm, Niraj H. ToliaAbstract:Plasmodium vivax and Plasmodium knowlesi invasion depends on the parasite Duffy-Binding protein DBL domain (RII-PvDBP or RII-PkDBP) engaging the Duffy antigen receptor for chemokines (DARC) on red blood cells. Inhibition of this key interaction provides an excellent opportunity for parasite control. There are competing models for whether Plasmodium ligands engage receptors as monomers or dimers, a question whose resolution has profound implications for parasite biology and control. We report crystallographic, solution and functional studies of RII-PvDBP showing that dimerization is required for and driven by receptor engagement. This work provides a unifying framework for prior studies and accounts for the action of naturally acquired blocking antibodies and the mechanism of immune evasion. We show that dimerization is conserved in DBL-domain receptor engagement and propose that receptor-mediated ligand dimerization drives receptor affinity and specificity. Because dimerization is prevalent in signaling, our studies raise the possibility that induced dimerization may activate pathways for invasion. Plasmodium parasites use Duffy-Binding Proteins (DBPs) to invade erythrocyte precursor cells via Binding to host protein DARC. Now this interaction is examined by structural and functional work on Plasmodium vivax DBP, revealing that it binds to DARC as a dimer and providing insights into host protective responses and immune evasion by the parasite.
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Dimerization of Plasmodium vivax DBP is induced upon receptor Binding and drives recognition of DARC
Nature Structural & Molecular Biology, 2011Co-Authors: Joseph D. Batchelor, Jacob A. Zahm, Niraj H. ToliaAbstract:Plasmodium parasites use Duffy-Binding Proteins (DBPs) to invade erythrocyte precursor cells via Binding to host protein DARC. Now this interaction is examined by structural and functional work on Plasmodium vivax DBP, revealing that it binds to DARC as a dimer and providing insights into host protective responses and immune evasion by the parasite.
Joseph D. Batchelor - One of the best experts on this subject based on the ideXlab platform.
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Dimerization of Plasmodium vivax DBP is induced upon receptor Binding and drives recognition of DARC
Nature Structural & Molecular Biology, 2011Co-Authors: Joseph D. Batchelor, Jacob A. Zahm, Niraj H. ToliaAbstract:Plasmodium vivax and Plasmodium knowlesi invasion depends on the parasite Duffy-Binding protein DBL domain (RII-PvDBP or RII-PkDBP) engaging the Duffy antigen receptor for chemokines (DARC) on red blood cells. Inhibition of this key interaction provides an excellent opportunity for parasite control. There are competing models for whether Plasmodium ligands engage receptors as monomers or dimers, a question whose resolution has profound implications for parasite biology and control. We report crystallographic, solution and functional studies of RII-PvDBP showing that dimerization is required for and driven by receptor engagement. This work provides a unifying framework for prior studies and accounts for the action of naturally acquired blocking antibodies and the mechanism of immune evasion. We show that dimerization is conserved in DBL-domain receptor engagement and propose that receptor-mediated ligand dimerization drives receptor affinity and specificity. Because dimerization is prevalent in signaling, our studies raise the possibility that induced dimerization may activate pathways for invasion. Plasmodium parasites use Duffy-Binding Proteins (DBPs) to invade erythrocyte precursor cells via Binding to host protein DARC. Now this interaction is examined by structural and functional work on Plasmodium vivax DBP, revealing that it binds to DARC as a dimer and providing insights into host protective responses and immune evasion by the parasite.
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Dimerization of Plasmodium vivax DBP is induced upon receptor Binding and drives recognition of DARC
Nature Structural & Molecular Biology, 2011Co-Authors: Joseph D. Batchelor, Jacob A. Zahm, Niraj H. ToliaAbstract:Plasmodium parasites use Duffy-Binding Proteins (DBPs) to invade erythrocyte precursor cells via Binding to host protein DARC. Now this interaction is examined by structural and functional work on Plasmodium vivax DBP, revealing that it binds to DARC as a dimer and providing insights into host protective responses and immune evasion by the parasite.
Michael Farzan - One of the best experts on this subject based on the ideXlab platform.
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sulphated tyrosines mediate association of chemokines and plasmodium vivax Duffy Binding protein with the Duffy antigen receptor for chemokines darc
Molecular Microbiology, 2005Co-Authors: Hyeryun Choe, Michael J Moore, Christopher M Owens, Paulette L Wright, Natalya Vasilieva, Wenhui Li, Agam P Singh, Rushdi Shakri, Chetan E Chitnis, Michael FarzanAbstract:Summary Plasmodium vivax is one of four Plasmodium species that cause human malaria. P. vivax and a related sim- ian malaria parasite, Plasmodium knowlesi , invade erythrocytes by Binding the Duffy antigen/receptor for chemokines (DARC) through their respective Duffy Binding Proteins. Here we show that tyrosines 30 and 41 of DARC are modified by addition of sulphate groups, and that the sulphated tyrosine 41 is essential for association of the Duffy Binding Proteins of P. vivax (PvDBP) and P. knowlesi (PkDaBP) with DARC- expressing cells. These sulphated tyrosines also par- ticipate in the association of DARC with each of its four known chemokine ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP-1, RANTES and MGSA association with DARC, but not with that of IL8. In contrast, alteration of tyrosine 30 to pheny- lalanine interferes with the association of IL8 with DARC. A soluble sulphated amino-terminal domain of DARC, but not one modified to phenylalanine at resi- due 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC 50 of approximately 5 nM. These data are consistent with a role for tyrosine sulphation in the association of
Chetan E Chitnis - One of the best experts on this subject based on the ideXlab platform.
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sulphated tyrosines mediate association of chemokines and plasmodium vivax Duffy Binding protein with the Duffy antigen receptor for chemokines darc
Molecular Microbiology, 2005Co-Authors: Hyeryun Choe, Michael J Moore, Christopher M Owens, Paulette L Wright, Natalya Vasilieva, Wenhui Li, Agam P Singh, Rushdi Shakri, Chetan E Chitnis, Michael FarzanAbstract:Summary Plasmodium vivax is one of four Plasmodium species that cause human malaria. P. vivax and a related sim- ian malaria parasite, Plasmodium knowlesi , invade erythrocytes by Binding the Duffy antigen/receptor for chemokines (DARC) through their respective Duffy Binding Proteins. Here we show that tyrosines 30 and 41 of DARC are modified by addition of sulphate groups, and that the sulphated tyrosine 41 is essential for association of the Duffy Binding Proteins of P. vivax (PvDBP) and P. knowlesi (PkDaBP) with DARC- expressing cells. These sulphated tyrosines also par- ticipate in the association of DARC with each of its four known chemokine ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP-1, RANTES and MGSA association with DARC, but not with that of IL8. In contrast, alteration of tyrosine 30 to pheny- lalanine interferes with the association of IL8 with DARC. A soluble sulphated amino-terminal domain of DARC, but not one modified to phenylalanine at resi- due 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC 50 of approximately 5 nM. These data are consistent with a role for tyrosine sulphation in the association of
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targeted deletion of plasmodium knowlesi Duffy Binding protein confirms its role in junction formation during invasion
Molecular Microbiology, 2005Co-Authors: Agam P Singh, Hastings Ozwara, Clemens H M Kocken, Sunil K Puri, Alan W Thomas, Chetan E ChitnisAbstract:Summary Red cell invasion by Plasmodium merozoites involves multiple steps such as attachment, apical reorienta- tion, junction formation and entry into a parasito- phorous vacuole. These steps are mediated by specific molecular interactions. P. vivax and the sim- ian parasite P. knowlesi require interaction with the Duffy blood group antigen to invade human erythro- cytes. P. vivax and P. knowlesi Duffy Binding Proteins (PvDBP and PkDBP), which bind the Duffy antigen during invasion, share regions of sequence homology and belong to a family of erythrocyte Binding Proteins (EBPs). By deletion of the gene that encodes PkDBP, we demonstrate that interaction of PkDBP with the Duffy antigen is absolutely necessary for invasion of human erythrocytes by P. knowlesi . Electron micros- copy studies reveal that PkDBP knockout parasites are unable to form a junction with human erythro- cytes. The interaction of PkDBP with the Duffy antigen is thus necessary for the critical step of junction for- mation during invasion. These studies provide sup- port for development of intervention strategies that target EBPs to inhibit junction formation and block erythrocyte invasion by malaria parasites.
Jacob A. Zahm - One of the best experts on this subject based on the ideXlab platform.
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Dimerization of Plasmodium vivax DBP is induced upon receptor Binding and drives recognition of DARC
Nature Structural & Molecular Biology, 2011Co-Authors: Joseph D. Batchelor, Jacob A. Zahm, Niraj H. ToliaAbstract:Plasmodium vivax and Plasmodium knowlesi invasion depends on the parasite Duffy-Binding protein DBL domain (RII-PvDBP or RII-PkDBP) engaging the Duffy antigen receptor for chemokines (DARC) on red blood cells. Inhibition of this key interaction provides an excellent opportunity for parasite control. There are competing models for whether Plasmodium ligands engage receptors as monomers or dimers, a question whose resolution has profound implications for parasite biology and control. We report crystallographic, solution and functional studies of RII-PvDBP showing that dimerization is required for and driven by receptor engagement. This work provides a unifying framework for prior studies and accounts for the action of naturally acquired blocking antibodies and the mechanism of immune evasion. We show that dimerization is conserved in DBL-domain receptor engagement and propose that receptor-mediated ligand dimerization drives receptor affinity and specificity. Because dimerization is prevalent in signaling, our studies raise the possibility that induced dimerization may activate pathways for invasion. Plasmodium parasites use Duffy-Binding Proteins (DBPs) to invade erythrocyte precursor cells via Binding to host protein DARC. Now this interaction is examined by structural and functional work on Plasmodium vivax DBP, revealing that it binds to DARC as a dimer and providing insights into host protective responses and immune evasion by the parasite.
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Dimerization of Plasmodium vivax DBP is induced upon receptor Binding and drives recognition of DARC
Nature Structural & Molecular Biology, 2011Co-Authors: Joseph D. Batchelor, Jacob A. Zahm, Niraj H. ToliaAbstract:Plasmodium parasites use Duffy-Binding Proteins (DBPs) to invade erythrocyte precursor cells via Binding to host protein DARC. Now this interaction is examined by structural and functional work on Plasmodium vivax DBP, revealing that it binds to DARC as a dimer and providing insights into host protective responses and immune evasion by the parasite.
