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Cryo-EM reveals the...
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Raghavan, Sai Sundar RajanUniversity of Copenhagen,Copenhagen University Hospital
(författare)
Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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2022-11-16
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Public Library of Science (PLoS),2022
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:ba0a19aa-67a5-480d-994b-ac14db1a16b4
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https://lup.lub.lu.se/record/ba0a19aa-67a5-480d-994b-ac14db1a16b4URI
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https://doi.org/10.1371/journal.ppat.1010924DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4’s broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Dagil, RobertCopenhagen University Hospital,University of Copenhagen
(författare)
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Lopez-Perez, MaryUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Conrad, JulianScience for Life Laboratory (SciLifeLab)
(författare)
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Bassi, Maria RosariaCopenhagen University Hospital,University of Copenhagen
(författare)
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del Pilar Quintana, MariaCopenhagen University Hospital,University of Copenhagen
(författare)
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Choudhary, SwatiCopenhagen University Hospital,University of Copenhagen
(författare)
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Gustavsson, TobiasCopenhagen University Hospital,University of Copenhagen
(författare)
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Wang, YongUniversity of Edinburgh,Zhejiang University
(författare)
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Gourdon, PontusLund University,Lunds universitet,Membranproteinstrukturbiologi,Forskargrupper vid Lunds universitet,Membrane Protein Structural Biology,Lund University Research Groups,University of Copenhagen(Swepub:lu)med-pgd
(författare)
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Ofori, Michael FokuoUniversity of Ghana
(författare)
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Christensen, Sebastian BojeUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Minja, Daniel Thomas RemiasNational Institute for Medical Research Tanga
(författare)
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Schmiegelow, ChristentzeUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Nielsen, Morten AgertougUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Barfod, LeaCopenhagen University Hospital,University of Copenhagen
(författare)
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Hviid, LarsUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Salanti, AliUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Lavstsen, ThomasUniversity of Copenhagen,Copenhagen University Hospital
(författare)
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Wang, KaituoUniversity of Copenhagen
(författare)
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University of CopenhagenCopenhagen University Hospital
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:PLoS Pathogens: Public Library of Science (PLoS)18:111553-73661553-7374
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Raghavan, Sai Su ...
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Dagil, Robert
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Lopez-Perez, Mar ...
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Conrad, Julian
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Bassi, Maria Ros ...
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del Pilar Quinta ...
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Choudhary, Swati
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Gustavsson, Tobi ...
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Wang, Yong
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Gourdon, Pontus
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Ofori, Michael F ...
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Christensen, Seb ...
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Minja, Daniel Th ...
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Schmiegelow, Chr ...
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Nielsen, Morten ...
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Barfod, Lea
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Hviid, Lars
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Salanti, Ali
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Lavstsen, Thomas
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Wang, Kaituo
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