Structural Basis of Karrikin and Non-natural Strigolactone Perception in Physcomitrella patens

In plants, strigolactones are perceived by the dual receptor-hydrolase DWARF14 (D14). D14 belongs to the superfamily of α/β hydrolases and is structurally similar to the karrikin receptor KARRIKIN INSENSITIVE 2 (KAI2). The moss Physcomitrella patens is an ideal model system for studying this receptor family, because it includes 11 highly related family members with unknown ligand specificity. We present the crystal structures of three Physcomitrella D14/KAI2-like proteins and describe a loop-based mechanism that leads to a permanent widening of the hydrophobic substrate gorge. We have identified protein clades that specifically perceive the karrikin KAR1 and the non-natural strigolactone isomer (−)-5-deoxystrigol in a highly stereoselective manner. [Display omitted] •Physcomitrella patens provides an early evolutionary snapshot of 11 KAI2-like proteins•A loop segment determines substrate specificity in Physcomitrella KAI2-like proteins•Distinct groups of proteins perceive (−)-5-deoxystrigol and the karrikin KAR1•Physcomitrella KAI2-like proteins cannot complement Arabidopsis kai2 or d14 mutants Bürger et al. dissect strigolactone and karrikin perception in the moss Physcomitrella patens, which first appeared on Earth 460 million years ago and provides an early evolutionary snapshot of 11 related receptor proteins. Three crystal structures reveal a loop-based mechanism that determines substrate specificity and affinity.