2c6j
From Proteopedia
(New page: 200px<br /><applet load="2c6j" size="450" color="white" frame="true" align="right" spinBox="true" caption="2c6j, resolution 3.Å" /> '''STRUCTURE OF P. KNOWLE...) |
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| - | [[Image:2c6j.gif|left|200px]]<br /><applet load="2c6j" size=" | + | [[Image:2c6j.gif|left|200px]]<br /><applet load="2c6j" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2c6j, resolution 3.Å" /> | caption="2c6j, resolution 3.Å" /> | ||
'''STRUCTURE OF P. KNOWLESI DBL DOMAIN CAPABLE OF BINDING HUMAN DUFFY ANTIGEN'''<br /> | '''STRUCTURE OF P. KNOWLESI DBL DOMAIN CAPABLE OF BINDING HUMAN DUFFY ANTIGEN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Molecular processes that govern pathogenic features of erythrocyte | + | Molecular processes that govern pathogenic features of erythrocyte invasion and cytoadherence in malaria are reliant on Plasmodium-specific Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize diverse host cell-surface receptors during pathogenesis. DBLs of parasite erythrocyte-binding proteins mediate invasion, and those from the antigenically variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) have been implicated in cytoadherence. The simian and human malarial parasites, P. knowlesi and P. vivax, invade human erythrocytes exclusively through the host DARC receptor (Duffy antigen receptor for chemokines). Here we present the crystal structure of the P. knowlesi DBL domain (Pkalpha-DBL), which binds to DARC during invasion of human erythrocytes. Pkalpha-DBL retains the overall fold observed in DBLs from P. falciparum erythrocyte-binding antigen (EBA)-175 (ref. 4). Mapping the residues that have previously been implicated in binding highlights a fairly flat but exposed site for DARC recognition in subdomain 2 of Pkalpha-DBL; this is in sharp contrast to receptor recognition by EBA-175 (ref. 4). In Pkalpha-DBL, the residues that contact DARC and the clusters of residues under immune pressure map to opposite surfaces of the DBL, and suggest a possible mechanism for immune evasion by P. vivax. Our comparative structural analysis of Pkalpha-DBL and P. falciparum EBA-175 provides a framework for the understanding of malaria parasite DBLs, and may affect the development of new prophylactic and therapeutic strategies. |
==About this Structure== | ==About this Structure== | ||
| - | 2C6J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_knowlesi Plasmodium knowlesi]. Full crystallographic information is available from [http:// | + | 2C6J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_knowlesi Plasmodium knowlesi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C6J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Hora, R.]] | [[Category: Hora, R.]] | ||
[[Category: Sharma, A.]] | [[Category: Sharma, A.]] | ||
| - | [[Category: Singh, S | + | [[Category: Singh, S K.]] |
[[Category: dbl domain]] | [[Category: dbl domain]] | ||
[[Category: duffy antigen]] | [[Category: duffy antigen]] | ||
[[Category: invasion]] | [[Category: invasion]] | ||
[[Category: malaria]] | [[Category: malaria]] | ||
| - | [[Category: p | + | [[Category: p knowlesi]] |
| - | [[Category: p | + | [[Category: p vivax]] |
[[Category: receptor]] | [[Category: receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:31 2008'' |
Revision as of 14:45, 21 February 2008
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STRUCTURE OF P. KNOWLESI DBL DOMAIN CAPABLE OF BINDING HUMAN DUFFY ANTIGEN
Overview
Molecular processes that govern pathogenic features of erythrocyte invasion and cytoadherence in malaria are reliant on Plasmodium-specific Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize diverse host cell-surface receptors during pathogenesis. DBLs of parasite erythrocyte-binding proteins mediate invasion, and those from the antigenically variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) have been implicated in cytoadherence. The simian and human malarial parasites, P. knowlesi and P. vivax, invade human erythrocytes exclusively through the host DARC receptor (Duffy antigen receptor for chemokines). Here we present the crystal structure of the P. knowlesi DBL domain (Pkalpha-DBL), which binds to DARC during invasion of human erythrocytes. Pkalpha-DBL retains the overall fold observed in DBLs from P. falciparum erythrocyte-binding antigen (EBA)-175 (ref. 4). Mapping the residues that have previously been implicated in binding highlights a fairly flat but exposed site for DARC recognition in subdomain 2 of Pkalpha-DBL; this is in sharp contrast to receptor recognition by EBA-175 (ref. 4). In Pkalpha-DBL, the residues that contact DARC and the clusters of residues under immune pressure map to opposite surfaces of the DBL, and suggest a possible mechanism for immune evasion by P. vivax. Our comparative structural analysis of Pkalpha-DBL and P. falciparum EBA-175 provides a framework for the understanding of malaria parasite DBLs, and may affect the development of new prophylactic and therapeutic strategies.
About this Structure
2C6J is a Single protein structure of sequence from Plasmodium knowlesi. Full crystallographic information is available from OCA.
Reference
Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain., Singh SK, Hora R, Belrhali H, Chitnis CE, Sharma A, Nature. 2006 Feb 9;439(7077):741-4. Epub 2005 Dec 21. PMID:16372020
Page seeded by OCA on Thu Feb 21 16:45:31 2008
Categories: Plasmodium knowlesi | Single protein | Belrhali, H. | Chitnis, C. | Hora, R. | Sharma, A. | Singh, S K. | Dbl domain | Duffy antigen | Invasion | Malaria | P knowlesi | P vivax | Receptor
