6mpv

From Proteopedia

(Difference between revisions)

Current revision

Cryo-electron microscopy structure of Plasmodium falciparum Rh5/CyRPA/Ripr invasion complex

6mpv, resolution 7.17Å

Structural highlights

6mpv is a 4 chain structure with sequence from Plasmodium falciparum and Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 7.17Å
Experimental data:	Check to display Experimental Data
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 the severe form of malaria that has high levels of mortality in humans. Blood-stage merozoites of P. falciparum invade erythrocytes, and this requires interactions between multiple ligands from the parasite and receptors in hosts. These interactions include the binding of the Rh5-CyRPA-Ripr complex with the erythrocyte receptor basigin(1,2), which is an essential step for entry into human erythrocytes. Here we show that the Rh5-CyRPA-Ripr complex binds the erythrocyte cell line JK-1 significantly better than does Rh5 alone, and that this binding occurs through the insertion of Rh5 and Ripr into host membranes as a complex with high molecular weight. We report a cryo-electron microscopy structure of the Rh5-CyRPA-Ripr complex at subnanometre resolution, which reveals the organization of this essential invasion complex and the mode of interactions between members of the complex, and shows that CyRPA is a critical mediator of complex assembly. Our structure identifies blades 4-6 of the beta-propeller of CyRPA as contact sites for Rh5 and Ripr. The limited contacts between Rh5-CyRPA and CyRPA-Ripr are consistent with the dissociation of Rh5 and Ripr from CyRPA for membrane insertion. A comparision of the crystal structure of Rh5-basigin with the cryo-electron microscopy structure of Rh5-CyRPA-Ripr suggests that Rh5 and Ripr are positioned parallel to the erythrocyte membrane before membrane insertion. This provides information on the function of this complex, and thereby provides insights into invasion by P. falciparum.

Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.,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 Nature. 2018 Dec 12. pii: 10.1038/s41586-018-0779-6. doi:, 10.1038/s41586-018-0779-6. PMID:30542156^[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
↑ 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

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/6mpv"

@@ Line 3: / Line 3: @@
 <SX load='6mpv' size='340' side='right' viewer='molstar' caption='[[6mpv]], [[Resolution|resolution]] 7.17&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mpv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7] and [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MPV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MPV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mpv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] and [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=6MPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MPV FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.17&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF3D7_0423800 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=6mpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mpv OCA], [https://pdbe.org/6mpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mpv RCSB], [https://www.ebi.ac.uk/pdbsum/6mpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mpv ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6mpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mpv OCA], [http://pdbe.org/6mpv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mpv RCSB], [http://www.ebi.ac.uk/pdbsum/6mpv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mpv 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 22: / Line 23: @@
 </SX>
 [[Category: Large Structures]]
-[[Category: Plaf7]]
+[[Category: Plasmodium falciparum]]
-[[Category: Plafa]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: Cowman, A F]]
+[[Category: Cowman AF]]
-[[Category: Wilson, W]]
+[[Category: Wilson W]]
-[[Category: Zhiheng, Y]]
+[[Category: Zhiheng Y]]
-[[Category: Cell invasion]]
-[[Category: Invasion ligand protein complex]]

6mpv

From Proteopedia

Current revision

Cryo-electron microscopy structure of Plasmodium falciparum Rh5/CyRPA/Ripr invasion complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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