Alkaloid binding to opium poppy major latex proteins triggers structural modification and functional aggregation

Opium poppy accumulates alkaloids in the specialized cytoplasm of laticifers known as latex. Here the authors show that the binding of alkaloids to the abundant major latex proteins triggers quaternary structural modification that mediates a functional role for protein aggregation. Opium poppy accumulates copious amounts of several benzylisoquinoline alkaloids including morphine, noscapine, and papaverine, in the specialized cytoplasm of laticifers, which compose an internal secretory system associated with phloem throughout the plant. The contiguous latex includes an abundance of related proteins belonging to the pathogenesis-related (PR)10 family known collectively as major latex proteins (MLPs) and representing at least 35% of the total cellular protein content. Two latex MLP/PR10 proteins, thebaine synthase and neopione isomerase, have recently been shown to catalyze late steps in morphine biosynthesis previously assigned as spontaneous reactions. Using a combination of sucrose density-gradient fractionation-coupled proteomics, differential scanning fluorimetry, isothermal titration calorimetry, and X-ray crystallography, we show that the major latex proteins are a family of alkaloid-binding proteins that display altered conformation in the presence of certain ligands. Addition of MLP/PR10 proteins to yeast strains engineered with morphine biosynthetic genes from the plant significantly enhanced the conversion of salutaridine to morphinan alkaloids.

Automated summary

This study reveals the functional role of major latex proteins in aiding opium poppy accumulate alkaloids through protein aggregation. Major latex proteins are a family of alkaloid-binding proteins that undergo conformational changes in the presence of specific ligands.