Structural basis for selective activation of ABA receptors. Nat Struct Mol Biol 2010 Sep;17(9):1109-13
Date
08/24/2010Pubmed ID
20729860Pubmed Central ID
PMC2933299DOI
10.1038/nsmb.1898Scopus ID
2-s2.0-77956341748 (requires institutional sign-in at Scopus site) 99 CitationsAbstract
Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discover its primary target PYR1, the founding member of the PYR/PYL family of soluble ABA receptors. To understand pyrabactin's selectivity, we have taken a combined structural, chemical and genetic approach. We show that subtle differences between receptor binding pockets control ligand orientation between productive and nonproductive modes. Nonproductive binding occurs without gate closure and prevents receptor activation. Observations in solution show that these orientations are in rapid equilibrium that can be shifted by mutations to control maximal agonist activity. Our results provide a robust framework for the design of new agonists and reveal a new mechanism for agonist selectivity.
Author List
Peterson FC, Burgie ES, Park SY, Jensen DR, Weiner JJ, Bingman CA, Chang CE, Cutler SR, Phillips GN Jr, Volkman BFAuthors
Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of WisconsinBrian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ArabidopsisArabidopsis Proteins
Membrane Transport Proteins
Models, Molecular
Mutation
Naphthalenes
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Structure, Tertiary
Sulfonamides
