Activating the Prolactin Receptor: Effect of the Ligand on the Conformation of the Extracellular Domain

作者：Groothuizen Flora S; Poger David; Mark Alan E^*

来源：Journal of Chemical Theory and Computation, 2010, 6(10): 3274-3283.

DOI：10.1021/ct1003934

The prolactin receptor resides on the surface of the cell as a preformed dimer. This suggests that cell signaling is triggered by conformational changes within the extracellular domain of the receptors. Here, by using atomistic molecular dynamics simulations, we show that the removal of the ligand placental lactogen from the dimeric form of the prolactin receptor results in a relative reorientation of the two extracellular domains by 20-30 degrees, which corresponds to a clockwise rotation of the domains with respect to each other. Such a mechanism of activation for the prolactin receptor is similar to that proposed previously in the case of the growth hormone receptor. In addition to the effect of the removal of the ligand, the mechanical coupling between the extracellular and transmembrane domains within a model membrane was also examined.

• 出版日期2010-10