3VDL: Crystal Structure Of Circumsporozoite Protein Atsr Domain, P43212 Form

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 "alphaTSR" domain. The alphaTSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but alphaTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized alphaTSR 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.
PDB ID: 3VDLDownload
MMDB ID: 99381
PDB Deposition Date: 2012/1/5
Updated in MMDB: 2012/05
Experimental Method:
x-ray diffraction
Resolution: 2.04  Å
Source Organism:
Similar Structures:
Biological Unit for 3VDL: monomeric; determined by author
Molecular Components in 3VDL
Label Count Molecule
Protein (1 molecule)
Circumsporozoite (Cs) Protein
Molecule annotation
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Citing MMDB