Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling

Structural view of a dynamic molecular switch mechanism that governs repression and activation of the jasmonate plant hormone pathway. The signalling pathway triggered by the plant hormone jasmonate regulates plant stress responses and also growth and development. At a molecular level, the jasmonate ZIM-domain (JAZ) proteins act as jasmonate co-receptors but also repress the activity of MYC transcription factors, which are required to convey the jasmonate signal. Sheng Yang He and colleagues use X-ray crystallography to address the question of how these same proteins can switch roles between transcriptional repressors and jasmonate co-receptors. Previous work had suggested that the conserved Jas motif of a JAZ repressor binds to jasmonate as a partially unwound helix. These authors find that the motif forms a complete α-helix on binding to MYC. Consequently, the Jas motif becomes an integral part of the MYC N-terminal fold resulting in a notable conformational change in MYC. This competitive binding inhibits MYC interaction with a subunit of the transcriptional Mediator complex, repressing its transcriptional activity. The plant hormone jasmonate plays crucial roles in regulating plant responses to herbivorous insects and microbial pathogens and is an important regulator of plant growth and development1,2,3,4,5,6,7. Key mediators of jasmonate signalling include MYC transcription factors, which are repressed by jasmonate ZIM-domain (JAZ) transcriptional repressors in the resting state. In the presence of active jasmonate, JAZ proteins function as jasmonate co-receptors by forming a hormone-dependent complex with COI1, the F-box subunit of an SCF-type ubiquitin E3 ligase8,9,10,11. The hormone-dependent formation of the COI1–JAZ co-receptor complex leads to ubiquitination and proteasome-dependent degradation of JAZ repressors and release of MYC proteins from transcriptional repression3,10,12. The mechanism by which JAZ proteins repress MYC transcription factors and how JAZ proteins switch between the repressor function in the absence of hormone and the co-receptor function in the presence of hormone remain enigmatic. Here we show that Arabidopsis MYC3 undergoes pronounced conformational changes when bound to the conserved Jas motif of the JAZ9 repressor. The Jas motif, previously shown to bind to hormone as a partly unwound helix, forms a complete α-helix that displaces the amino (N)-terminal helix of MYC3 and becomes an integral part of the MYC N-terminal fold. In this position, the Jas helix competitively inhibits MYC3 interaction with the MED25 subunit of the transcriptional Mediator complex. Our structural and functional studies elucidate a dynamic molecular switch mechanism that governs the repression and activation of a major plant hormone pathway.