Mechanistic basis for enhanced strigolactone sensitivity in KAI2 triple mutant

Striga hermonthica is a parasitic weed that destroys billions of dollars’
worth of staple crops every year. Its rapid proliferation stems from an
enhanced ability to metabolize strigolactones (SLs), plant hormones that
direct root branching and shoot growth. Striga’s SL receptor, ShHTL7,
bears more similarity to the staple crop karrikin receptor KAI2 than to SL
receptor D14, though KAI2 variants in plants like Arabidopsis thaliana
show minimal SL sensitivity. Recently, studies have indicated that a small
number of point mutations to HTL7 residues can confer SL sensitivity to
AtKAI2. Here, we analyze both wild-type AtKAI2 and SL-sensitive mutant
Var64 through all-atom, long-timescale molecular dynamics simulations to
determine the effects of these mutations on receptor function at a
molecular level. We demonstrate that the mutations stabilize SL binding by
about 2 kcal/mol. They also result in a doubling of the average pocket
volume and eliminate the dependence of binding on certain pocket
conformational arrangements. While the probability of certain non-binding
SL-receptor interactions increases in the mutant compared with the
wild-type, the rate of binding also increases by a factor of ten. All
these changes account for the increased SL sensitivity in mutant KAI2 and
suggest mechanisms for increasing functionality of host crop SL receptors.