Crystal structure of human ERK1 bound to a peptide corresponding to the sequence of the Toxoplasma gondii effector protein GRA24 KIM1 sequence at 2.17 Å resolution

The causative agent of toxoplasmosis, the intracellular parasite Toxoplasma gondii, delivers a protein, GRA24, into the cells it infects that interacts with the mitogen-activated protein (MAP) kinase p38α (MAPK14), leading to activation and nuclear translocation of the host kinase and a subsequent inflammatory response that controls the progress of the parasite. This protein also binds the MAP kinase ERK1. We have determined the structure of ERK1 in complex with a peptide with the sequence of the KIM1 motif of GRA24. We have used this sequence to stabilise a complex between ERK2 and its activating MAP2K MEK1 allowing structure determination by cryoEM. The crystal structure provided high resolution confirmation of the GRA24 KIM1 sequence to ERK1.

刚地弓形虫（Toxoplasma gondii）是弓形虫病的病原体，这种胞内寄生虫会向其所感染的宿主细胞内递送一种名为GRA24的蛋白质。该蛋白可与丝裂原活化蛋白（MAP）激酶p38α（MAPK14）相互作用，引发宿主激酶的激活与核转位，并触发后续的炎症反应，从而调控寄生虫的增殖进程。此外，GRA24还能与MAP激酶ERK1结合。我们解析了ERK1与携带GRA24的KIM1基序序列的肽段所形成复合物的晶体结构。我们利用该KIM1基序序列稳定了ERK2与其激活型MAP2K MEK1之间的复合物，进而通过冷冻电镜（cryoEM）完成了该复合物的结构解析。上述晶体结构为GRA24的KIM1序列与ERK1的相互作用提供了高分辨率的验证。