5tik

From Proteopedia

(Difference between revisions)

Current revision

Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA

Structural highlights

5tik is a 4 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.09Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CYRPA_PLAF7 Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:22593616, PubMed:25583518, PubMed:27374406, PubMed:28195038, PubMed:28195530). Required for the assembly of the PfRH5 adhesion complex (or invasion complex) composed of CyRPA, RH5 and RIPR at the interface between the merozoite and the host erythrocyte membranes (PubMed:25583518, PubMed:28186186, PubMed:28195038, PubMed:28195530, PubMed:30542156). This facilitates the binding of RH5 to host receptor BSG/basigin, which leads to the establishment of a tight junction between the merozoite and host erythrocyte membranes and allows Ca(2+) release into the erythrocyte (PubMed:27374406, PubMed:28186186, PubMed:30542156).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Plasmodium falciparum causes malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of erythrocytes by merozoites, in which they grow and divide to release daughter merozoites, which in turn invade new erythrocytes perpetuating the cycle responsible for malaria. A key step in merozoite invasion is the essential binding of PfRh5/CyRPA/PfRipr complex to basigin, a step linked to formation of a pore between merozoites and erythrocytes. We show CyRPA interacts directly with PfRh5. An invasion inhibitory monoclonal antibody to CyRPA blocks binding of CyRPA to PfRh5 and complex formation thus illuminating the molecular mechanism for inhibition of parasite growth. We determined the crystal structures of CyRPA alone and in complex with antibody Fab fragment. CyRPA has a six-bladed beta-propeller fold, and we identify the region that interacts with PfRh5. This functionally conserved epitope is a potential target for vaccines against P. falciparum.

Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA.,Chen L, Xu Y, Wong W, Thompson JK, Healer J, Goddard-Borger E, Lawrence MC, Cowman AF Elife. 2017 Feb 14;6. pii: e21347. doi: 10.7554/eLife.21347. PMID:28195530^[8]

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

References

↑ Dreyer AM, Matile H, Papastogiannidis P, Kamber J, Favuzza P, Voss TS, Wittlin S, Pluschke G. Passive immunoprotection of Plasmodium falciparum-infected mice designates the CyRPA as candidate malaria vaccine antigen. J Immunol. 2012 Jun 15;188(12):6225-37. PMID:22593616 doi:10.4049/jimmunol.1103177
↑ Reddy KS, Amlabu E, Pandey AK, Mitra P, Chauhan VS, Gaur D. Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion. Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1179-84. PMID:25583518 doi:10.1073/pnas.1415466112
↑ Volz JC, Yap A, Sisquella X, Thompson JK, Lim NT, Whitehead LW, Chen L, Lampe M, Tham WH, Wilson D, Nebl T, Marapana D, Triglia T, Wong W, Rogers KL, Cowman AF. Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes. Cell Host Microbe. 2016 Jul 13;20(1):60-71. PMID:27374406 doi:10.1016/j.chom.2016.06.004
↑ Galaway F, Drought LG, Fala M, Cross N, Kemp AC, Rayner JC, Wright GJ. P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5. Nat Commun. 2017 Feb 10;8:14333. PMID:28186186 doi:10.1038/ncomms14333
↑ Favuzza P, Guffart E, Tamborrini M, Scherer B, Dreyer AM, Rufer AC, Erny J, Hoernschemeyer J, Thoma R, Schmid G, Gsell B, Lamelas A, Benz J, Joseph C, Matile H, Pluschke G, Rudolph MG. Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody. Elife. 2017 Feb 14;6. pii: e20383. doi: 10.7554/eLife.20383. PMID:28195038 doi:http://dx.doi.org/10.7554/eLife.20383
↑ Chen L, Xu Y, Wong W, Thompson JK, Healer J, Goddard-Borger E, Lawrence MC, Cowman AF. Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. Elife. 2017 Feb 14;6. pii: e21347. doi: 10.7554/eLife.21347. PMID:28195530 doi:http://dx.doi.org/10.7554/eLife.21347
↑ Wong W, Huang R, Menant S, Hong C, Sandow JJ, Birkinshaw RW, Healer J, Hodder AN, Kanjee U, Tonkin CJ, Heckmann D, Soroka V, Sogaard TMM, Jorgensen T, Duraisingh MT, Czabotar PE, de Jongh WA, Tham WH, Webb AI, Yu Z, Cowman AF. Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. Nature. 2018 Dec 12. pii: 10.1038/s41586-018-0779-6. doi:, 10.1038/s41586-018-0779-6. PMID:30542156 doi:http://dx.doi.org/10.1038/s41586-018-0779-6
↑ Chen L, Xu Y, Wong W, Thompson JK, Healer J, Goddard-Borger E, Lawrence MC, Cowman AF. Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. Elife. 2017 Feb 14;6. pii: e21347. doi: 10.7554/eLife.21347. PMID:28195530 doi:http://dx.doi.org/10.7554/eLife.21347

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/5tik"

@@ Line 1: / Line 1: @@
 ==Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA==
-<StructureSection load='5tik' size='340' side='right' caption='[[5tik]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
+<StructureSection load='5tik' size='340' side='right'caption='[[5tik]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tik]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TIK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TIK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tik]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TIK FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tih|5tih]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.09&#8491;</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=5tik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tik OCA], [http://pdbe.org/5tik PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tik RCSB], [http://www.ebi.ac.uk/pdbsum/5tik PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tik ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tik OCA], [https://pdbe.org/5tik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tik RCSB], [https://www.ebi.ac.uk/pdbsum/5tik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tik ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/CYRPA_PLAF7 CYRPA_PLAF7] Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:22593616, PubMed:25583518, PubMed:27374406, PubMed:28195038, PubMed:28195530). Required for the assembly of the PfRH5 adhesion complex (or invasion complex) composed of CyRPA, RH5 and RIPR at the interface between the merozoite and the host erythrocyte membranes (PubMed:25583518, PubMed:28186186, PubMed:28195038, PubMed:28195530, PubMed:30542156). This facilitates the binding of RH5 to host receptor BSG/basigin, which leads to the establishment of a tight junction between the merozoite and host erythrocyte membranes and allows Ca(2+) release into the erythrocyte (PubMed:27374406, PubMed:28186186, PubMed:30542156).<ref>PMID:22593616</ref> <ref>PMID:25583518</ref> <ref>PMID:27374406</ref> <ref>PMID:28186186</ref> <ref>PMID:28195038</ref> <ref>PMID:28195530</ref> <ref>PMID:30542156</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Chen, L]]
+[[Category: Large Structures]]
-[[Category: Cowman, A F]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: Goddard-Borger, E]]
+[[Category: Chen L]]
-[[Category: Lawrence, M C]]
+[[Category: Cowman AF]]
-[[Category: Thompson, J K]]
+[[Category: Goddard-Borger E]]
-[[Category: Wang, W]]
+[[Category: Lawrence MC]]
-[[Category: Xu, Y]]
+[[Category: Thompson JK]]
-[[Category: Immune system]]
+[[Category: Wang W]]
-[[Category: Plasmodium falciparum cyrpa inhibitory antibody]]
+[[Category: Xu Y]]

5tik

From Proteopedia

Current revision

Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox