7JGF

Cryo-EM structure of P. falciparum VAR2CSA FCR3 domains DBL5 and DBL6 at 4.69 A

7JGF の概要

• エントリーDOI: 10.2210/pdb7jgf/pdb
• EMDBエントリー: 22323 22324 22325 22326 22327
• 分子名称: Erythrocyte membrane protein 1 (1 entity in total)
• 機能のキーワード: placental malaria, var2csa, duffy binding domain, csa, pfemp1, sugar binding protein
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 308823.19

構造登録者

Ma, R.,Tolia, N.H. (登録日: 2020-07-19, 公開日: 2021-01-13, 最終更新日: 2025-06-04)

主引用文献

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

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: 33452495
DOI: 10.1038/s41564-020-00858-9

実験手法

ELECTRON MICROSCOPY (4.69 Å)