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Cryo-EM structures of anti-malarial antibody L9 with circumsporozoite protein reveal trimeric L9 association and complete 27-residue epitope.
Tripathi, Prabhanshu; Bender, Michael F; Lei, Haotian; Da Silva Pereira, Lais; Shen, Chen-Hsiang; Bonilla, Brian; Dillon, Marlon; Ou, Li; Pancera, Marie; Wang, Lawrence T; Zhang, Baoshan; Batista, Facundo D; Idris, Azza H; Seder, Robert A; Kwong, Peter D.
Afiliación
  • Tripathi P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bender MF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lei H; Research Technology Branch Electron Microscopy Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Da Silva Pereira L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Shen CH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bonilla B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Dillon M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ou L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pancera M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Wang LT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Batista FD; Departments of Immunology and Microbiology, Harvard Medical School, Boston, MA 02139, USA.
  • Idris AH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Seder RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.
Structure ; 31(4): 480-491.e4, 2023 04 06.
Article en En | MEDLINE | ID: mdl-36931276
ABSTRACT
Monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein (PfCSP) and is highly protective following controlled human malaria challenge. To gain insight into its function, we determined cryoelectron microscopy (cryo-EM) structures of L9 in complex with full-length PfCSP and assessed how this recognition influenced protection by wild-type and mutant L9s. Cryo-EM reconstructions at 3.6- and 3.7-Å resolution revealed L9 to recognize PfCSP as an atypical trimer. Each of the three L9s in the trimer directly recognized an Asn-Pro-Asn-Val (NPNV) tetrapeptide on PfCSP and interacted homotypically to facilitate L9-trimer assembly. We analyzed peptides containing different repeat tetrapeptides for binding to wild-type and mutant L9s to delineate epitope and homotypic components of L9 recognition; we found both components necessary for potent malaria protection. Last, we found the 27-residue stretch recognized by L9 to be highly conserved in P. falciparum isolates, suggesting the newly revealed complete L9 epitope to be an attractive vaccine target.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vacunas contra la Malaria / Malaria / Antimaláricos Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Structure Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA / BIOTECNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vacunas contra la Malaria / Malaria / Antimaláricos Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Structure Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA / BIOTECNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos