Activation Mechanism of Strigolactone Receptors and Its Impact on Ligand Selectivity between Host and Parasitic Plants.

Parasitic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate hydrolysis followed by a conformational change of the receptor to a "closed" or "active" state that associates with a signaling partner, MAX2/D3. Crystal structures of active and inactive At D14 receptors have helped elucidate the structural changes involved in activation. However, the mechanism by which the receptor activates remains unknown. The ligand dependence of At D14 activation has been disputed by mutagenesis studies showing that enzymatically inactive receptors are able to associate with MAX2 proteins. Furthermore, activation differences between strigolactone receptor in Striga , Sh HTL7, and At D14 could contribute to the high sensitivity to strigolactones exhibited by parasitic plants. Using molecular dynamics simulations, we demonstrate that both At D14 and Sh HTL7 could adopt an active conformation in the absence of ligand. However, Sh HTL7 exhibits a higher population in the inactive apo state as compared to the At D14 receptor. We demonstrate that this difference in inactive state population is caused by sequence differences between their D-loops and interactions with the catalytic histidine that prevent full binding pocket closure in Sh HTL7. These results indicate that ligand hydrolysis would enhance the active state population by destabilizing the inactive state in Sh HTL7 as compared to At D14. We also show that the mechanism of activation is more concerted in At D14 than in Sh HTL7 and that the main barrier to activation in Sh HTL7 is closing of the binding pocket.