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Publications of the Week

Structural Plasticity of D3-D14 Ubiquitin Ligase in Strigolactone Signalling

By December 3, 2018No Comments

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This week we profile a recent publication in Nature from the laboratory of
Dr. Ning Zheng (pictured) in the Department of Pharmacaology at the University of Washington.

Can you provide a brief overview of your lab’s current research focus?

One major focus of our research is to understand the role of selective protein destruction in eukaryotic biology and human diseases. Just like protein synthesis, protein degradation is tightly controlled in all eukaryotic organisms and is frequently involved in the regulation of diverse cellular functions. We are interested in dissecting how different cellular signals induce specific protein degradation in human cells, thereby mediating various biological processes, such as cell cycle progression, tissue differentiation, stress response, and circadian rhythm. We are also curious about how the naturally occurring plant hormones dictate plant growth and development by triggering protein degradation and transcription reprogramming. Our late studies on plant hormone signaling have helped us formulate a novel “molecular glue” concept, which we are currently applying to the development of new therapeutic compounds through targeted protein degradation.

What is the significance of the findings in this publication?

This publication is part of our continuous studies of plant hormones. Strigolactones are a newly identified class of plant hormones that regulate a variety of functions in plant physiology, including shoot branching, root development, symbiotic interactions with fungi, and seed germination of parasitic plants. Its receptor has recently been mapped to a protein complex, which not only senses and translates the hormonal signal to selective degradation of transcription regulators, but also metabolizes and terminates it. Using a combination of structural biology and biochemical approaches, we discovered a large degree of structural plasticity within this protein complex, which helps coordinate hormone perception, signal transduction, and hormone metabolism. By providing deeper insights into the molecular mechanisms of strigolactone signaling, our findings can potentially impact crop production and agriculture in the future.

What are the next steps for this research?

Next, we would like to determine all conformational states adopted by the strigoractone-sensing protein complex and understand their temporal relationship. We also wonder whether a similar protein complex exists outside the green kingdom.

This research was funded by:

We are supported by Howard Hughes Medical Institute. Our collaborator, Dr. Ottoline Leyser, in the Sainsbury Laboratory at University of Cambridge is supported by the Gatsby Charitable Foundation and the European Research Council.

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