Crystal structure of circumsporozoite protein aTSR domain in complex with 1710 antibodyCrystal structure of circumsporozoite protein aTSR domain in complex with 1710 antibody

Structural highlights

6b0s is a 3 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:X-ray diffraction, Resolution 1.95Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSP_PLAFO The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host).

Publication Abstract from PubMed

Antibodies against the central repeat of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, the humoral response to the PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP from European donors who underwent immunization with live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies were specific for C-PfCSP, highlighting the rare occurrence of C-PfCSP-reactive B cells in PfSPZ-CVac-induced protective immunity. These two antibodies showed poor sporozoite binding and weak inhibition of parasite traversal and development, and did not protect mice from infection with PfCSP transgenic Plasmodium berghei sporozoites. Structural analyses demonstrated that one antibody interacts with a polymorphic region overlapping two T cell epitopes, suggesting that variability in C-PfCSP may benefit parasite escape from humoral and cellular immunity. Our data identify important features underlying C-PfCSP shortcomings as a vaccine target.

Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection.,Scally SW, Murugan R, Bosch A, Triller G, Costa G, Mordmuller B, Kremsner PG, Sim BKL, Hoffman SL, Levashina EA, Wardemann H, Julien JP J Exp Med. 2017 Nov 22. pii: jem.20170869. doi: 10.1084/jem.20170869. PMID:29167197[1]

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

See Also

References

  1. Scally SW, Murugan R, Bosch A, Triller G, Costa G, Mordmuller B, Kremsner PG, Sim BKL, Hoffman SL, Levashina EA, Wardemann H, Julien JP. Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection. J Exp Med. 2017 Nov 22. pii: jem.20170869. doi: 10.1084/jem.20170869. PMID:29167197 doi:http://dx.doi.org/10.1084/jem.20170869

6b0s, resolution 1.95Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA