The Hormel Institute’s CryoEM is used to fight antibiotic resistance

Published 3:01 pm Saturday, May 9, 2020

A new discovery based on research using The Hormel Institute’s powerful electron microscope – the CryoEM – was published by Dr. Bin Liu, head of the Transcription and Gene Regulation lab. Dr. Liu’s research offers new understanding of how an important process in gene transcription works.

Gene transcription is the process in which DNA is copied into RNA, allowing the gene to create things like proteins that do jobs in our bodies. Transcription activation is the process that increases gene transcription of some genes. Cyclic AMP receptor protein (CAP) is a major transcription activator.

Although CAP has been studied for decades, it is still unclear whether and how CAP remodels RNA polymerase (RNAP) to activate transcription. RNA polymerase is an enzyme that does the work of copying DNA into RNA during gene transcription.

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Using cryo-EM, Dr. Liu and his team have captured an on-pathway intermediate state with significant changes to the shape of the protein during transcription activation. The structural information gained in this study suggests a unique CAP-induced activation mechanism that significantly widens the main cleft of RNAP. This makes it easier for DNA promoters to enter into the cleft and form the open promoter complex, where the double strand of DNA is unwound so it can be transcribed.

“This study will advance the structural understanding of bacterial transcription activation, benefit the prokaryotic transcription research field and offer a new idea to cope with bacterial antibiotic resistance,” said Dr. Liu. “Resistance to antibiotics is rising to dangerously high levels in all parts of the world and threatening our ability to treat common infectious diseases.  We will study the mechanisms of transcription activation by other transcriptional factors, too. Drugs that target and trap the intermediate state could be screened to treat bacterial infections, especially antibiotic-resistant ‘superbugs’”.

Dr. Liu’s article, “Visualization of two architectures in class-II CAP-dependent transcription activation” was published in the prestigious top journal PLOS Biology. PLOS Biology is the flagship PLOS journal in the life sciences and features works of exceptional significance, originality, and relevance in all areas of biological science.