7rm0: Difference between revisions
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==== | ==Antibody 2E10.E9 in complex with P. vivax CSP peptide ANGAGNQPGANGAGNQPG== | ||
<StructureSection load='7rm0' size='340' side='right'caption='[[7rm0]]' scene=''> | <StructureSection load='7rm0' size='340' side='right'caption='[[7rm0]], [[Resolution|resolution]] 2.71Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7rm0]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RM0 FirstGlance]. <br> | ||
</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=7rm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rm0 OCA], [https://pdbe.org/7rm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rm0 RCSB], [https://www.ebi.ac.uk/pdbsum/7rm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rm0 ProSAT]</span></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]] 2.71Å</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=7rm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rm0 OCA], [https://pdbe.org/7rm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rm0 RCSB], [https://www.ebi.ac.uk/pdbsum/7rm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rm0 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q2TM01_PLAVI Q2TM01_PLAVI] Essential sporozoite protein (By similarity). 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 (By similarity). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes.[ARBA:ARBA00033715] Essential sporozoite protein. In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands. In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes. Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes.[RuleBase:RU369056] 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.[RuleBase:RU369056] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Malaria is a global health burden, with Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) responsible for the majority of infections worldwide. Circumsporozoite protein (CSP) is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection. Although much has been uncovered about the molecular basis of antibody recognition of the PfCSP repeats, data remains scarce for PvCSP. Here, we performed molecular dynamics simulations for peptides comprising the PvCSP repeats from strains VK210 and VK247 to reveal how the PvCSP central repeats are highly disordered, with minor propensities to adopt turn conformations. Next, we solved eight crystal structures to unveil the interactions of two inhibitory monoclonal antibodies (mAbs), 2F2 and 2E10.E9, with PvCSP repeats. Both antibodies can accommodate subtle sequence variances in the repeat motifs and recognize largely coiled peptide conformations that also contain isolated turns. Our structural studies uncover various degrees of Fab-Fab homotypic interactions upon recognition of the PvCSP central repeats by these two inhibitory mAbs, similar to potent mAbs against PfCSP. These findings augment our understanding of host-Plasmodium interactions and contribute molecular details of Pv inhibition by mAbs to unlock structure-based engineering of PvCSP-based vaccines. | |||
Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats.,Kucharska I, Hossain L, Ivanochko D, Yang Q, Rubinstein JL, Pomes R, Julien JP Elife. 2022 Jan 13;11:e72908. doi: 10.7554/eLife.72908. PMID:35023832<ref>PMID:35023832</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rm0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Plasmodium vivax]] | |||
[[Category: Ivanochko D]] | |||
[[Category: Julien JP]] | |||
[[Category: Kucharska I]] | |||
Revision as of 19:33, 18 October 2023
Antibody 2E10.E9 in complex with P. vivax CSP peptide ANGAGNQPGANGAGNQPGAntibody 2E10.E9 in complex with P. vivax CSP peptide ANGAGNQPGANGAGNQPG
Structural highlights
FunctionQ2TM01_PLAVI Essential sporozoite protein (By similarity). 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 (By similarity). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes.[ARBA:ARBA00033715] Essential sporozoite protein. In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands. In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes. Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes.[RuleBase:RU369056] 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.[RuleBase:RU369056] Publication Abstract from PubMedMalaria is a global health burden, with Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) responsible for the majority of infections worldwide. Circumsporozoite protein (CSP) is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection. Although much has been uncovered about the molecular basis of antibody recognition of the PfCSP repeats, data remains scarce for PvCSP. Here, we performed molecular dynamics simulations for peptides comprising the PvCSP repeats from strains VK210 and VK247 to reveal how the PvCSP central repeats are highly disordered, with minor propensities to adopt turn conformations. Next, we solved eight crystal structures to unveil the interactions of two inhibitory monoclonal antibodies (mAbs), 2F2 and 2E10.E9, with PvCSP repeats. Both antibodies can accommodate subtle sequence variances in the repeat motifs and recognize largely coiled peptide conformations that also contain isolated turns. Our structural studies uncover various degrees of Fab-Fab homotypic interactions upon recognition of the PvCSP central repeats by these two inhibitory mAbs, similar to potent mAbs against PfCSP. These findings augment our understanding of host-Plasmodium interactions and contribute molecular details of Pv inhibition by mAbs to unlock structure-based engineering of PvCSP-based vaccines. Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats.,Kucharska I, Hossain L, Ivanochko D, Yang Q, Rubinstein JL, Pomes R, Julien JP Elife. 2022 Jan 13;11:e72908. doi: 10.7554/eLife.72908. PMID:35023832[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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