4HQF: Crystal Structure Of Plasmodium Falciparum Trap, I4 Form

Sporozoite gliding motility and invasion of mosquito and vertebrate host cells in malaria is mediated by thrombospondin repeat anonymous protein (TRAP). Tandem von Willebrand factor A (VWA) and thrombospondin type I repeat (TSR) domains in TRAP connect through proline-rich stalk, transmembrane, and cytoplasmic domains to the parasite actin-dependent motility apparatus. We crystallized fragments containing the VWA and TSR domains from Plasmodium vivax and Plasmodium falciparum in different crystal lattices. TRAP VWA domains adopt closed and open conformations, and bind a Mg(2+) ion at a metal ion-dependent adhesion site implicated in ligand binding. Metal ion coordination in the open state is identical to that seen in the open high-affinity state of integrin I domains. The closed VWA conformation associates with a disordered TSR domain. In contrast, the open VWA conformation crystallizes with an extensible beta ribbon and ordered TSR domain. The extensible beta ribbon is composed of disulfide-bonded segments N- and C-terminal to the VWA domain that are largely drawn out of the closed VWA domain in a 15 A movement to the open conformation. The extensible beta ribbon and TSR domain overlap at a conserved interface. The VWA, extensible beta ribbon, and TSR domains adopt a highly elongated overall orientation that would be stabilized by tensile force exerted across a ligand-receptor complex by the actin motility apparatus of the sporozoite. Our results provide insights into regulation of "stick-and-slip" parasite motility and for development of sporozoite subunit vaccines.
PDB ID: 4HQFDownload
MMDB ID: 106241
PDB Deposition Date: 2012/10/25
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4HQF: monomeric; determined by author and by software (PISA)
Molecular Components in 4HQF
Label Count Molecule
Protein (1 molecule)
Thrombospondin-related Anonymous Protein, Trap
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB