6mb3: Difference between revisions

Latest revision as of 13:11, 23 October 2024

Cryo-EM structure of the circumsporozoite protein of Plasmodium falciparum with a vaccine-elicited antibody reveals maturation of inter-antibody contactsCryo-EM structure of the circumsporozoite protein of Plasmodium falciparum with a vaccine-elicited antibody reveals maturation of inter-antibody contacts

6mb3, resolution 3.37Å

Structural highlights

6mb3 is a 19 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.37Å
Experimental data:	Check
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSP_PLAF7 Essential sporozoite protein (PubMed:29554084, PubMed:32150583). In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands (By similarity). In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes (PubMed:29554084, PubMed:32150583). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity).[UniProtKB:P23093]^[1] ^[2] In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.[UniProtKB:P23093]

Publication Abstract from PubMed

The circumsporozoite protein (CSP) on the surface of Plasmodium falciparum sporozoites is important for parasite development, motility, and host hepatocyte invasion. However, intrinsic disorder of the NANP repeat sequence in the central region of CSP has hindered its structural and functional characterization. Here, the cryo-electron microscopy structure at ~3.4-A resolution of a recombinant shortened CSP construct with the variable domains (Fabs) of a highly protective monoclonal antibody reveals an extended spiral conformation of the central NANP repeat region surrounded by antibodies. This unusual structure appears to be stabilized and/or induced by interaction with an antibody where contacts between adjacent Fabs are somatically mutated and enhance the interaction. This maturation in non-antigen contact residues may be an effective mechanism for antibodies to target tandem repeat sequences and provide novel insights into malaria vaccine design.

Cryo-EM structure of P. falciparum circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts.,Oyen D, Torres JL, Cottrell CA, Richter King C, Wilson IA, Ward AB Sci Adv. 2018 Oct 10;4(10):eaau8529. doi: 10.1126/sciadv.aau8529. eCollection, 2018 Oct. PMID:30324137^[3]

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

References

↑ Tan J, Sack BK, Oyen D, Zenklusen I, Piccoli L, Barbieri S, Foglierini M, Fregni CS, Marcandalli J, Jongo S, Abdulla S, Perez L, Corradin G, Varani L, Sallusto F, Sim BKL, Hoffman SL, Kappe SHI, Daubenberger C, Wilson IA, Lanzavecchia A. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. Nat Med. 2018 Mar 19. pii: nm.4513. doi: 10.1038/nm.4513. PMID:29554084 doi:http://dx.doi.org/10.1038/nm.4513
↑ Oyen D, Torres JL, Aoto PC, Flores-Garcia Y, Binter S, Pholcharee T, Carroll S, Reponen S, Wash R, Liang Q, Lemiale F, Locke E, Bradley A, King CR, Emerling D, Kellam P, Zavala F, Ward AB, Wilson IA. Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein. PLoS Pathog. 2020 Mar 9;16(3):e1008373. doi: 10.1371/journal.ppat.1008373. PMID:32150583 doi:http://dx.doi.org/10.1371/journal.ppat.1008373
↑ Oyen D, Torres JL, Cottrell CA, Richter King C, Wilson IA, Ward AB. Cryo-EM structure of P. falciparum circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts. Sci Adv. 2018 Oct 10;4(10):eaau8529. doi: 10.1126/sciadv.aau8529. eCollection, 2018 Oct. PMID:30324137 doi:http://dx.doi.org/10.1126/sciadv.aau8529

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OCA

[1] Tan J, Sack BK, Oyen D, Zenklusen I, Piccoli L, Barbieri S, Foglierini M, Fregni CS, Marcandalli J, Jongo S, Abdulla S, Perez L, Corradin G, Varani L, Sallusto F, Sim BKL, Hoffman SL, Kappe SHI, Daubenberger C, Wilson IA, Lanzavecchia A. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. Nat Med. 2018 Mar 19. pii: nm.4513. doi: 10.1038/nm.4513. PMID:29554084 doi:http://dx.doi.org/10.1038/nm.4513

[2] Oyen D, Torres JL, Aoto PC, Flores-Garcia Y, Binter S, Pholcharee T, Carroll S, Reponen S, Wash R, Liang Q, Lemiale F, Locke E, Bradley A, King CR, Emerling D, Kellam P, Zavala F, Ward AB, Wilson IA. Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein. PLoS Pathog. 2020 Mar 9;16(3):e1008373. doi: 10.1371/journal.ppat.1008373. PMID:32150583 doi:http://dx.doi.org/10.1371/journal.ppat.1008373

[3] Oyen D, Torres JL, Cottrell CA, Richter King C, Wilson IA, Ward AB. Cryo-EM structure of P. falciparum circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts. Sci Adv. 2018 Oct 10;4(10):eaau8529. doi: 10.1126/sciadv.aau8529. eCollection, 2018 Oct. PMID:30324137 doi:http://dx.doi.org/10.1126/sciadv.aau8529

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <SX load='6mb3' size='340' side='right' viewer='molstar' caption='[[6mb3]], [[Resolution|resolution]] 3.37&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mb3]] is a 19 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MB3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mb3]] is a 19 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MB3 FirstGlance]. <br>
-</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=6mb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb3 OCA], [http://pdbe.org/6mb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb3 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb3 ProSAT]</span></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]] 3.37&#8491;</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=6mb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb3 OCA], [https://pdbe.org/6mb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mb3 RCSB], [https://www.ebi.ac.uk/pdbsum/6mb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb3 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/CSP_PLAF7 CSP_PLAF7] Essential sporozoite protein (PubMed:29554084, PubMed:32150583). In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands (By similarity). In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes (PubMed:29554084, PubMed:32150583). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity).[UniProtKB:P23093]<ref>PMID:29554084</ref> <ref>PMID:32150583</ref>   In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.[UniProtKB:P23093]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 </div>
 <div class="pdbe-citations 6mb3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>
 __TOC__
 </SX>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Cottrell, C A]]
-[[Category: Torres, J L]]
-[[Category: Ward, A B]]
-[[Category: Antibody]]
-[[Category: Csp]]
-[[Category: Immune system]]
 [[Category: Plasmodium falciparum]]
-[[Category: Rscsp]]
+[[Category: Cottrell CA]]
+[[Category: Torres JL]]
+[[Category: Ward AB]]

6mb3: Difference between revisions

Latest revision as of 13:11, 23 October 2024

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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6mb3: Difference between revisions

Latest revision as of 13:11, 23 October 2024

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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