3VDK

Crystal structure of circumsporozoite protein aTSR domain, R32 platinum-bound form

Summary for 3VDK

• Entry DOI: 10.2210/pdb3vdk/pdb
• Related: 3VDJ 3VDL
• Descriptor: Circumsporozoite (CS) protein, PLATINUM (II) ION (3 entities in total)
• Functional Keywords: tsr, atsr, cell invasion
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 1
• Total formula weight: 9097.15

Authors

Doud, M.B.,Koksal, A.C.,Mi, L.Z.,Song, G.,Lu, C.,Springer, T.A. (deposition date: 2012-01-05, release date: 2012-05-09, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.847 Å)