4nuu

From Proteopedia

(Difference between revisions)

Revision as of 10:55, 25 December 2014

Heterotrimer structure of Region II from Plasmodium vivax Duffy Binding Protein (PvDBP) bound to the ectodomain of the Duffy Antigen Receptor for Chemokines (DARC)

Structural highlights

4nuu is a 3 chain structure with sequence from Human and Plavs. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4nuv
Gene:	PVDR (PLAVS), DARC, ACKR1, FY, GPD (HUMAN)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PVDR_PLAVS] Binds to the human erythrocytes Duffy blood group determinant. [ACKR1_HUMAN] Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.

Publication Abstract from PubMed

Plasmodium parasites use specialized ligands which bind to red blood cell (RBC) receptors during invasion. Defining the mechanism of receptor recognition is essential for the design of interventions against malaria. Here, we present the structural basis for Duffy antigen (DARC) engagement by P. vivax Duffy binding protein (DBP). We used NMR to map the core region of the DARC ectodomain contacted by the receptor binding domain of DBP (DBP-RII) and solved two distinct crystal structures of DBP-RII bound to this core region of DARC. Isothermal titration calorimetry studies show these structures are part of a multi-step binding pathway, and individual point mutations of residues contacting DARC result in a complete loss of RBC binding by DBP-RII. Two DBP-RII molecules sandwich either one or two DARC ectodomains, creating distinct heterotrimeric and heterotetrameric architectures. The DARC N-terminus forms an amphipathic helix upon DBP-RII binding. The studies reveal a receptor binding pocket in DBP and critical contacts in DARC, reveal novel targets for intervention, and suggest that targeting the critical DARC binding sites will lead to potent disruption of RBC engagement as complex assembly is dependent on DARC binding. These results allow for models to examine inter-species infection barriers, Plasmodium immune evasion mechanisms, P. knowlesi receptor-ligand specificity, and mechanisms of naturally acquired P. vivax immunity. The step-wise binding model identifies a possible mechanism by which signaling pathways could be activated during invasion. It is anticipated that the structural basis of DBP host-cell engagement will enable development of rational therapeutics targeting this interaction.

Red Blood Cell Invasion by Plasmodium vivax: Structural Basis for DBP Engagement of DARC.,Batchelor JD, Malpede BM, Omattage NS, Dekoster GT, Henzler-Wildman KA, Tolia NH PLoS Pathog. 2014 Jan;10(1):e1003869. doi: 10.1371/journal.ppat.1003869. Epub, 2014 Jan 9. PMID:24415938^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Batchelor JD, Malpede BM, Omattage NS, Dekoster GT, Henzler-Wildman KA, Tolia NH. Red Blood Cell Invasion by Plasmodium vivax: Structural Basis for DBP Engagement of DARC. PLoS Pathog. 2014 Jan;10(1):e1003869. doi: 10.1371/journal.ppat.1003869. Epub, 2014 Jan 9. PMID:24415938 doi:http://dx.doi.org/10.1371/journal.ppat.1003869

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nuu"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nuu RCSB], [http://www.ebi.ac.uk/pdbsum/4nuu PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PVDR_PLAVS PVDR_PLAVS]] Binds to the human erythrocytes Duffy blood group determinant. [[http://www.uniprot.org/uniprot/ACKR1_HUMAN ACKR1_HUMAN]] Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4nuu

From Proteopedia

Revision as of 10:55, 25 December 2014

Heterotrimer structure of Region II from Plasmodium vivax Duffy Binding Protein (PvDBP) bound to the ectodomain of the Duffy Antigen Receptor for Chemokines (DARC)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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