7JGF
Cryo-EM structure of P. falciparum VAR2CSA FCR3 domains DBL5 and DBL6 at 4.69 A
Summary for 7JGF
| Entry DOI | 10.2210/pdb7jgf/pdb |
| EMDB information | 22323 22324 22325 22326 22327 |
| Descriptor | Erythrocyte membrane protein 1 (1 entity in total) |
| Functional Keywords | placental malaria, var2csa, duffy binding domain, csa, pfemp1, sugar binding protein |
| Biological source | Plasmodium falciparum |
| Total number of polymer chains | 1 |
| Total formula weight | 308823.19 |
| Authors | Ma, R.,Tolia, N.H. (deposition date: 2020-07-19, release date: 2021-01-13, Last modification date: 2024-11-20) |
| Primary citation | Ma, R.,Lian, T.,Huang, R.,Renn, J.P.,Petersen, J.D.,Zimmerberg, J.,Duffy, P.E.,Tolia, N.H. Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA. Nat Microbiol, 6:380-391, 2021 Cited by PubMed Abstract: Plasmodium falciparum VAR2CSA binds to chondroitin sulfate A (CSA) on the surface of the syncytiotrophoblast during placental malaria. This interaction facilitates placental sequestration of malaria parasites resulting in severe health outcomes for both the mother and her offspring. Furthermore, CSA is presented by diverse cancer cells and specific targeting of cells by VAR2CSA may become a viable approach for cancer treatment. In the present study, we determined the cryo-electron microscopy structures of the full-length ectodomain of VAR2CSA from P. falciparum strain NF54 in complex with CSA, and VAR2CSA from a second P. falciparum strain FCR3. The architecture of VAR2CSA is composed of a stable core flanked by a flexible arm. CSA traverses the core domain by binding within two channels and CSA binding does not induce major conformational changes in VAR2CSA. The CSA-binding elements are conserved across VAR2CSA variants and are flanked by polymorphic segments, suggesting immune selection outside the CSA-binding sites. This work provides paths for developing interventions against placental malaria and cancer. PubMed: 33452495DOI: 10.1038/s41564-020-00858-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.69 Å) |
Structure validation
Download full validation report
