Event
BIOE Seminar: Bacterial Outer Membrane Protein Assembly: A Tale of Two Inhibitors
Friday, October 23, 2026
9:00 a.m.
A. James Clark Hall, Room #2121
Sara Molinari
saramol@umd.edu
Harris Bernstein
Senior Investigator
National Institute of Diabetes and Digestive and Kidney Diseases
How a Conserved Molecular Machine Catalyzes the assembly of bacterial outer membrane proteins: a tale of two inhibitors
Abstract
Although integral membrane proteins that reside in most biological membranes contain one or more hydrophobic ⍺-helical membrane spanning segments, proteins that reside in the outer membrane of Gram-negative bacteria (e.g., E. coli, Salmonella) contain a unique structure called a “β barrel” that serves as a membrane anchor. From a bioengineering perspective, bacterial outer membrane proteins are of interest because they can be used as display platforms and biosensors. It is now clear that the folding and membrane insertion (“assembly”) of outer membrane proteins is catalyzed by the β barrel assembly machine (BAM), an essential heterooligomer that has been shown to be an excellent target for novel antibiotics. The most functionally significant subunit of BAM, BamA, is itself a β barrel protein that has some unusual properties. Using biochemical and structural approaches, we showed that BamA forms hybrid barrels with newly synthesized outer membrane proteins and thereby promotes their structural transition from a β sheet to a closed β barrel. Recently, we have been able to use peptides that inhibit BamA function to obtain new insights into the outer membrane protein assembly process and to discern how cells adapt to BAM dysfunction.
Bio
Dr. Bernstein received a Ph.D. from MIT in 1987, where he was one of the first scientists to use a cDNA clone of an RNA virus (poliovirus) to introduce site-directed mutations into the viral genome to elucidate the function of individual genes. He then worked as a post-doctoral fellow at UCSF, where he cloned and sequenced the gene that encodes the signal peptide binding subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that targets nascent secretory proteins to the endoplasmic reticulum. At the time SRP was thought to exist only in mammalian cells, but his work unexpectedly led to the discovery of an SRP homolog in E. coli. After joining the NIH faculty in 1993, he and his coworkers deciphered the function of bacterial SRP, and through their work they were able to explain why SRP had not been discovered in multiple genetic screens for components of the protein secretion machinery. In 2001 his group started to work on “autotransporters”, a widespread superfamily of virulence factors located in the outer membrane of Gram-negative bacteria. In a series of studies Dr. Bernstein’s group disproved the prevailing view that autotransporters form self-contained protein secretion systems and showed that autotransporters have features that make them outstanding model proteins to study outer membrane protein biogenesis. Recently Dr. Bernstein has turned his attention to the function of the β barrel assembly machine (BAM), a conserved factor that catalyzes the folding and membrane insertion of outer membrane proteins, as well as the role of membrane lipids in outer membrane protein biogenesis.
