Structural highlights
Publication Abstract from PubMed
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.
Unexpected fold in the circumsporozoite protein target of malaria vaccines.,Doud MB, Koksal AC, Mi LZ, Song G, Lu C, Springer TA Proc Natl Acad Sci U S A. 2012 Apr 30. PMID:22547819[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Doud MB, Koksal AC, Mi LZ, Song G, Lu C, Springer TA. Unexpected fold in the circumsporozoite protein target of malaria vaccines. Proc Natl Acad Sci U S A. 2012 Apr 30. PMID:22547819 doi:10.1073/pnas.1205737109
