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Structural basis for selective activation of ABA receptors. Nat Struct Mol Biol 2010 Sep;17(9):1109-13

Date

08/24/2010

Pubmed ID

20729860

Pubmed Central ID

PMC2933299

DOI

10.1038/nsmb.1898

Scopus ID

2-s2.0-77956341748   72 Citations

Abstract

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 BF

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Arabidopsis
Arabidopsis Proteins
Membrane Transport Proteins
Models, Molecular
Mutation
Naphthalenes
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Structure, Tertiary
Sulfonamides
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46