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Publications of the Week

High-Throughput Identification of Dominant Negative Polypeptides in Yeast

By April 24, 2019No Comments

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This week we profile a recent publication in Nature Methods from
Drs. Michael Dorrity (pictured) and Stanley Fields at the University of Washington.

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

We work on developing new technologies, especially those that analyze protein activities.

What is the significance of the findings in this publication?

Protein can have modular function that is encoded in multiple distinct domains or interaction interfaces. The finding that many small fragments of native proteins can inhibit their full-length counterparts suggests that this modularity introduces a vulnerability. By screening in high-throughput for polypeptide fragments that inhibit protein function, we exploit this vulnerability, which might lead to identifying optimal inhibitors for many target proteins. Thus, this method should be useful in the development of small polypeptide therapeutics.

What are the next steps for this research?

We hope to use this method to find inhibitors for many protein targets – some of which may be otherwise challenging to target through small molecule-based drugs – resulting in large datasets of dominant negative polypeptides. We can then use such large datasets to learn about protein folding and the minimal features required for a fragment’s specificity for binding to its target.

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