4jrn

Publication Abstract from PubMed

At least a third of the human population is infected with the intracellular parasite Toxoplasma gondii, which contributes significantly to the disease burden in immunocompromised and neutropenic hosts and causes serious congenital complications when vertically transmitted to the fetus. Genetic analyses have identified the Toxoplasma ROP18 Ser/Thr protein kinase as a major factor mediating acute virulence in mice. ROP18 is secreted into the host cell during the invasion process, and its catalytic activity is required for the acute virulence phenotype. However, its precise molecular function and regulation are not fully understood. We have determined the crystal structure of the ROP18 kinase domain, which is inconsistent with a previously proposed autoinhibitory mechanism of regulation. Furthermore, a sucrose molecule bound to our structure identifies an additional ligand-binding pocket outside of the active site cleft. Mutational analysis confirms an important role for this pocket in virulence.

Structure of the Toxoplasma gondii ROP18 kinase domain reveals a second ligand binding pocket required for acute virulence.,Lim D, Gold DA, Julien L, Rosowski EE, Niedelman W, Yaffe MB, Saeij JP J Biol Chem. 2013 Nov 29;288(48):34968-80. doi: 10.1074/jbc.M113.523266. Epub, 2013 Oct 15. PMID:24129568^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.