Unknown

Dataset Information

0

Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii.


ABSTRACT: Serine/threonine kinases secreted from rhoptry organelles constitute important virulence factors of Toxoplasma gondii. Rhoptry kinases are highly divergent and their structures and regulatory mechanism are hitherto unknown. Here, we report the X-ray crystal structures of two related pseudokinases named ROP2 and ROP8, which differ primarily in their substrate-binding site. ROP kinases contain a typical bilobate kinase fold and a novel N-terminal extension that both stabilizes the N-lobe and provides a unique means of regulation. Although ROP2 and ROP8 were catalytically inactive, they provided a template for homology modelling of the active kinase ROP18, a major virulence determinant of T. gondii. Autophosphorylation of key residues in the N-terminal extension resulted in ROP18 activation, which in turn phosphorylated ROP2 and ROP8. Mutagenesis and mass spectrometry experiments revealed that ROP18 was maximally activated when this phosphorylated N-terminus relieved autoinhibition resulting from extension of aliphatic side chains into the ATP-binding pocket. This novel means of regulation governs ROP kinases implicated in parasite virulence.

SUBMITTER: Qiu W 

PROVIDER: S-EPMC2670854 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii.

Qiu Wei W   Wernimont Amy A   Tang Keliang K   Taylor Sonya S   Lunin Vladimir V   Schapira Matthieu M   Fentress Sarah S   Hui Raymond R   Sibley L David LD  

The EMBO journal 20090205 7


Serine/threonine kinases secreted from rhoptry organelles constitute important virulence factors of Toxoplasma gondii. Rhoptry kinases are highly divergent and their structures and regulatory mechanism are hitherto unknown. Here, we report the X-ray crystal structures of two related pseudokinases named ROP2 and ROP8, which differ primarily in their substrate-binding site. ROP kinases contain a typical bilobate kinase fold and a novel N-terminal extension that both stabilizes the N-lobe and provi  ...[more]

Similar Datasets

| S-EPMC3946946 | biostudies-literature
| S-EPMC2725553 | biostudies-literature
| S-EPMC6369123 | biostudies-literature
| S-EPMC4959664 | biostudies-literature
| S-EPMC3375832 | biostudies-literature
| S-EPMC8213820 | biostudies-literature
| S-EPMC2532663 | biostudies-literature
| S-EPMC1797617 | biostudies-literature
| S-EPMC10774369 | biostudies-literature
| S-EPMC4863586 | biostudies-other