Chemical Biology Seminar: Professor Bil Clemons, Caltech
About the Seminar
Multum in Parvo: Mechanisms of phage derived protein antibiotics
A key step in the bacteriophage life cycle is the requirement to breach the peptidoglycan layer of the bacterial cell wall. While a variety of lysis mechanisms have evolved, the simplest are found in single stranded DNA or RNA bacteriophages that, constrained by the small size of their genomes, encode a single gene lysis (SGL) protein. The first discovered and most studied example is Protein E from ΦX174 in the Microviridae family; a 91 amino acid peptide with a single transmembrane domain at its N-terminus. Protein E expression, dependent on the host chaperone SlyD, is sufficient for lysis of bacteria via inhibition of the phospho-MurNAc-pentapeptide translocase MraY, an essential enzyme in the biosynthesis of peptidoglycan. Despite the historic importance of ΦX174, the lysis mechanism remains poorly defined. Using single particle electron cryo-microscopy, we have demonstrated that Protein E forms a stable inhibitory complex with both E. coli MraY and SlyD by physically blocking access to the active site of MraY. The structure of this three-protein complex has additionally allowed us to derive new functional insight for both SlyD and MraY. Overall, the work provides exciting implications for the development of novel therapeutics.
About the Speaker
Bil Clemons is the Hanisch Memorial Professor of Biochemistry at Caltech and the Program Officer for Diversity in Science at the Chan Zuckerberg Initiative (CZI). He received his PhD from the University of Utah, where he worked under Prof. Venki Ramakrishnan. During this time, Prof. Clemons spent two years as a visiting scientist at the Laboratory of Molecular Biology in Cambridge, England. The most notable achievement during his graduate work was that he was part of the team that solved the first atomic resolution structure of the small ribosomal subunit, which led to a fundamental understanding of the translation of the genetic code and the Nobel Prize for his advisor. Following that, he became a Damon-Runyon Cancer Research post-doctoral fellow at Harvard Medical School, working for Profs. Tom Rapoport and Steve Harrison. During this time, he solved the structure of the ubiquitous protein translocation channel. Prof. Clemons began his independent group at Caltech in 2006. The focus of the Clemons lab is to characterize critical biological systems using a variety of techniques, including structural biology and biochemistry. The Clemons lab has contributed significantly to understanding membrane protein biogenesis, glycochemistry in lipid bilayers, and the development of novel antibacterial therapeutics. Prof. Clemons has received numerous awards, including being elected to the United States National Academy of Science in 2022, a fellow of the American Society of Biochemistry and Molecular Biology in 2022, a Searle Scholar in 2007, and the NIH Director’s Pioneer Award in 2011. He is a renowned mentor known for his extensive contributions to diversity, equity, and inclusion and has received one of Caltech’s two highest honors, The Shirley Malcom Prize for Mentoring (2024). In August 2023, he joined the CZI Science team, where he oversees a variety of funding programs, including the Science Diversity Leadership Award.