3VDJ

Crystal structure of circumsporozoite protein aTSR domain, R32 native form

3VDJ の概要

• エントリーDOI: 10.2210/pdb3vdj/pdb
• 関連するPDBエントリー: 3VDK 3VDL
• 分子名称: Circumsporozoite (CS) protein (2 entities in total)
• 機能のキーワード: tsr, atsr, cell invasion
• 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: 8902.08

構造登録者

Doud, M.B.,Koksal, A.C.,Mi, L.Z.,Song, G.,Lu, C.,Springer, T.A. (登録日: 2012-01-05, 公開日: 2012-05-09, 最終更新日: 2024-10-16)

主引用文献

Doud, M.B.,Koksal, A.C.,Mi, L.Z.,Song, G.,Lu, C.,Springer, T.A.
Unexpected fold in the circumsporozoite protein target of malaria vaccines.
Proc.Natl.Acad.Sci.USA, 109:7817-7822, 2012

PubMed Abstract: Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an "αTSR" domain. The αTSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but αTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized αTSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.

PubMed: 22547819
DOI: 10.1073/pnas.1205737109

実験手法

X-RAY DIFFRACTION (1.698 Å)