Title : Crystal
structure of autotaxin and insight into
GPCR activation by lipid mediators
Abstract :
- Autotaxin ( ATX , also known as Enpp2 ) is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine to generate lysophosphatidic acid ( LPA ), a lipid mediator that activates G protein-coupled receptors to evoke various cellular responses
- Here, we report the crystal structures of mouse ATX alone and in complex with LPAs with different acyl-chain lengths and saturations
- These structures reveal that the multidomain architecture helps to maintain the structural rigidity of the lipid-binding pocket, which accommodates the respective LPA molecules in distinct conformations
- They indicate that a loop region in the catalytic domain is a major determinant for the substrate specificity of the Enpp family enzymes
- Furthermore, along with biochemical and biological data, these structures suggest that the produced LPAs are delivered from the active site to cognate G protein-coupled receptors through a hydrophobic channel