Structural analysis of a ligand-triggered intermolecular disulfide switch in a major latex protein from opium poppy
Samuel C. Carr, Peter J. Facchini, Kenneth K.S. Ng [1]
Molecular Tour
Pathogenesis related 10 proteins have to been shown to bind the alkaloids of opium poppy and are suspected to be involved in their storage in the latex of specialized cells called ‘laticifers’. PR10-10 is a highly abundant protein in the latex of opium poppy and is known to bind alkaloids such as papaverine. The crystal structure of PR10-10 reveals how the binding of papaverine to the central hydrophobic cavity of the protein leads to large conformational changes in the structure of PR10-10. Binding of papaverine leads to the ordering of the cap-loop which sequesters the bound alkaloid. Ordering of the cap-loop changes the shape and size of the central cavity though the partial unwinding of an alpha-helix and ordering of a beta-strand. Beta-strand ordering leads to the burying of a cysteine sidechain which otherwise forms an intermolecular disulfide bond with other PR10-10 proteins. The structure of three cysteine to serine mutants of PR10-10 further demonstrate the importance of the intermolecular disulfide bond. When the disulfide bond forming cysteines 59 and 155 in PR10-10 are mutated to serine, thus unable to form disulfide bonds, the cap-loop of PR10-10 remains ordered, and the central cavity always occupied by a ligand. This demonstrates how the presence of the alkaloid changes not only the local structure of PR10-10 but also its ability to interact more widely with nearby proteins. The formation of intermolecular disulfide bonds in PR10-10 is predicted to be coupled to the large-scale organization of PR10 proteins and subsequent storage of high concentrations of alkaloids within protein aggregates in the latex of opium poppy.
References
- ↑ Carr SC, Facchini PJ, Ng KKS. Structural analysis of a ligand-triggered intermolecular disulfide switch in a major latex protein from opium poppy. Acta Crystallogr D Struct Biol. 2024 Sep 1;80(Pt 9):675-685. PMID:39207895 doi:10.1107/S2059798324007733
