7NNH

Cryo-EM structure of VAR2CSA FCR3 domain DBL5/6

7NNH の概要

• エントリーDOI: 10.2210/pdb7nnh/pdb
• 関連するPDBエントリー: 7B52 7B54
• EMDBエントリー: 12017 12018 12477
• 分子名称: Erythrocyte membrane protein 1 (1 entity in total)
• 機能のキーワード: var2csa, cell adhesion, malaria, pfemp1, dbl
• 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: 307549.81

構造登録者

Wang, K.T.,Dagil, R.,Salanti, A.,Gourdon, P.E. (登録日: 2021-02-24, 公開日: 2021-06-02, 最終更新日: 2025-07-09)

主引用文献

Wang, K.,Dagil, R.,Lavstsen, T.,Misra, S.K.,Spliid, C.B.,Wang, Y.,Gustavsson, T.,Sandoval, D.R.,Vidal-Calvo, E.E.,Choudhary, S.,Agerbaek, M.O.,Lindorff-Larsen, K.,Nielsen, M.A.,Theander, T.G.,Sharp, J.S.,Clausen, T.M.,Gourdon, P.,Salanti, A.
Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding.
Nat Commun, 12:2956-2956, 2021

PubMed Abstract: Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines.

PubMed: 34011972
DOI: 10.1038/s41467-021-23254-1

実験手法

ELECTRON MICROSCOPY (4 Å)