2FLG

Solution structure of an EGF-LIKE domain from the Plasmodium falciparum merozoite surface protein 1

2FLG の概要

• エントリーDOI: 10.2210/pdb2flg/pdb
• 関連するPDBエントリー: 1CEJ
• NMR情報: BMRB: 7010
• 分子名称: Merozoite surface protein 1 (1 entity in total)
• 機能のキーワード: egf-like domain, extracellular, modular protein, surface antigen, malaria vaccine component, surface protein, surface active protein
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P04933
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5600.31

構造登録者

James, S.,Moehle, K.,Pluschke, G.,Robinson, J. (登録日: 2006-01-06, 公開日: 2006-02-21, 最終更新日: 2024-11-06)

主引用文献

James, S.,Moehle, K.,Renard, A.,Mueller, M.S.,Vogel, D.,Zurbriggen, R.,Pluschke, G.,Robinson, J.A.
Synthesis, solution structure and immune recognition of an epidermal growth factor-like domain from Plasmodium falciparum merozoite surface protein-1.
Chembiochem, 7:1943-1950, 2006

PubMed Abstract: The Plasmodium falciparum merozoite surface protein-1 19 kDa fragment (MSP-1(19)) comprises two closely packed EGF-like domains (EGF=epidermal growth factor), each stabilized by three disulfide bonds. The native conformation of this protein is important for eliciting P. falciparum growth inhibitory antibodies. Here we show that the N-terminal EGF domain alone can be chemically synthesized and efficiently refolded to a native-like state, as shown by its solution structure as determined by NMR spectroscopy. In order to study its immunogenicity, the domain was coupled through its N terminus to a phospholipid and incorporated into reconstituted influenza virus-like particles (virosomes). When used to immunize mice, the peptide-loaded virosomes elicited potent humoral immune responses that were shown by Western blots and immunofluorescence assays to cross-react with native MSP-1 on the surfaces of P. falciparum blood stage parasites. This opens the way for a medicinal chemistry-oriented approach to the study and optimization of the antigenicity of the protein as a potential malaria vaccine candidate, whilst exploiting the immunopotentiating properties of influenza virosomes as a delivery vehicle.

PubMed: 17068840
DOI: 10.1002/cbic.200600357

実験手法

SOLUTION NMR