The Regulation Mechanism Of PINK1's Kinase Domain Associated With Parkinson's Disease

PINK1 is a highly conserved serine threonine kinase that primarily localizes to the mitochondria.PINK1 gene is a Parkinson's disease PD-related susceptibility gene PARK6 and belongs to one of the autosomal recessive inherited Parkinson's disease gene.Abnormality of this pathogenic gene will lead to various molecular and cellular biological changes such as mitochondrial dysfunction,ubiquitin-proteasome system(UPS)dysfunction,oxidative stress,and neuronal synaptic vesicle dysfunction,resulting in the occurrence of PD.Crystal structures with resolutions of 2.78 ? TcPINK1 and 3.1 ? PhPINK1 have been resolved.Elucidation of the importance of kinase domain INS3 and C-terminal(CTE)for the biological activity and substrate recognition of PINK1.However,it remains unclear how the activation mechanism of PINK1 and CTE affect the activity of kinase domain.This information is of great significance for clarifying its regulatory mechanism and pathogenic mechanism.In order to elucidate the mechanism of the bilolgical activity of PINK1 kinase,this study established PINK1 expression and purification system and PINK1 kinase activity detection system to study the key structural elements.