5mza

From Proteopedia

(Difference between revisions)

Revision as of 16:24, 22 March 2017

The DBLb domain of PF11_0521 PfEMP1 bound to human ICAM-1

Structural highlights

5mza is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ICAM1_HUMAN] ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. In case of rhinovirus infection acts as a cellular receptor for the virus.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria.

Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria.,Lennartz F, Adams Y, Bengtsson A, Olsen RW, Turner L, Ndam NT, Ecklu-Mensah G, Moussiliou A, Ofori MF, Gamain B, Lusingu JP, Petersen JE, Wang CW, Nunes-Silva S, Jespersen JS, Lau CK, Theander TG, Lavstsen T, Hviid L, Higgins MK, Jensen AT Cell Host Microbe. 2017 Mar 8;21(3):403-414. doi: 10.1016/j.chom.2017.02.009. PMID:28279348^[5]

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

References

↑ Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, Kamarck ME, McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839-47. PMID:2538243
↑ Marlin SD, Staunton DE, Springer TA, Stratowa C, Sommergruber W, Merluzzi VJ. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature. 1990 Mar 1;344(6261):70-2. PMID:1968231 doi:http://dx.doi.org/10.1038/344070a0
↑ Hayashi T, Takahashi T, Motoya S, Ishida T, Itoh F, Adachi M, Hinoda Y, Imai K. MUC1 mucin core protein binds to the domain 1 of ICAM-1. Digestion. 2001;63 Suppl 1:87-92. PMID:11173916
↑ van Buul JD, Allingham MJ, Samson T, Meller J, Boulter E, Garcia-Mata R, Burridge K. RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration. J Cell Biol. 2007 Sep 24;178(7):1279-93. Epub 2007 Sep 17. PMID:17875742 doi:10.1083/jcb.200612053
↑ Lennartz F, Adams Y, Bengtsson A, Olsen RW, Turner L, Ndam NT, Ecklu-Mensah G, Moussiliou A, Ofori MF, Gamain B, Lusingu JP, Petersen JE, Wang CW, Nunes-Silva S, Jespersen JS, Lau CK, Theander TG, Lavstsen T, Hviid L, Higgins MK, Jensen AT. Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria. Cell Host Microbe. 2017 Mar 8;21(3):403-414. doi: 10.1016/j.chom.2017.02.009. PMID:28279348 doi:http://dx.doi.org/10.1016/j.chom.2017.02.009

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/5mza"

Categories: Higgins, M K | Lennartz, F | Cell adhesion | Pfemp1 icam-1 cerebral malaria

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5mza is ON HOLD  until Paper Publication
+==The DBLb domain of PF11_0521 PfEMP1 bound to human ICAM-1==
+<StructureSection load='5mza' size='340' side='right' caption='[[5mza]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5mza]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MZA FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PO:TRIPHOSPHATE'>3PO</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<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=5mza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mza OCA], [http://pdbe.org/5mza PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mza RCSB], [http://www.ebi.ac.uk/pdbsum/5mza PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mza ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ICAM1_HUMAN ICAM1_HUMAN]] ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. In case of rhinovirus infection acts as a cellular receptor for the virus.<ref>PMID:2538243</ref> <ref>PMID:1968231</ref> <ref>PMID:11173916</ref> <ref>PMID:17875742</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria.
-Authors: Lennartz, F., Higgins, M.K.
+Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria.,Lennartz F, Adams Y, Bengtsson A, Olsen RW, Turner L, Ndam NT, Ecklu-Mensah G, Moussiliou A, Ofori MF, Gamain B, Lusingu JP, Petersen JE, Wang CW, Nunes-Silva S, Jespersen JS, Lau CK, Theander TG, Lavstsen T, Hviid L, Higgins MK, Jensen AT Cell Host Microbe. 2017 Mar 8;21(3):403-414. doi: 10.1016/j.chom.2017.02.009. PMID:28279348<ref>PMID:28279348</ref>
-Description: The DBLb domain of PF11_0521 PfEMP1 bound to human ICAM-1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Higgins, M.K]]
+<div class="pdbe-citations 5mza" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Higgins, M K]]
 [[Category: Lennartz, F]]
+[[Category: Cell adhesion]]
+[[Category: Pfemp1 icam-1 cerebral malaria]]

5mza

From Proteopedia

Revision as of 16:24, 22 March 2017

The DBLb domain of PF11_0521 PfEMP1 bound to human ICAM-1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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