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Title – Cryo-EM of Helical Polymers at Near-Atomic Resolution Yields Surprises: From Microbial Nanowires to Indestructible Pili
Host – Allon Hochbaum
Biosketch – Edward Egelman is a biophysicist known for his work on the structure and function of protein and nucleoprotein polymers. He developed the algorithm that is now widely used in cryo-electron microscopy for the three-dimensional reconstruction of helical filaments and tubes. His research has ranged from studies of actin to bacterial pili to viruses that infect hosts living in nearly boiling acid. Egelman was born in New York and graduated from Brandeis University in 1976 with a B.A. in physics. He started as a Ph.D. student in experimental high energy physics at Harvard, but changed fields and received his Ph.D. from Brandeis University in 1982 in biophysics. He was a Jane Coffin Childs postdoctoral fellow at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, and became an Assistant Professor at Yale University in 1984. In 1989 he moved to the University of Minnesota where he was an Associate and Full Professor, and in 1999 moved to the University of Virginia where he is now a Harrison Distinguished Professor. He has been president of the Biophysical Society and Editor-in-Chief of Biophysical Journal, and is a Fellow of both the Biophysical Society and the American Academy of Microbiology. In 2019 he was elected to the National Academy of Sciences.
Abstract – Large amounts of protein in eukaryotic, bacterial and archaeal cells is often found in the form of helical polymers. Viruses infecting these cells can also be helical. We have been using cryo-EM to study the structure and function of many of these polymers. Since the introduction of direct electron detectors about six years ago, there has been a “resolution revolution” where near-atomic levels of resolution can now almost routinely be achieved for many macromolecular complexes. While some of these complexes can, in principle, be crystallized, cryo-EM has emerged as the method of choice for structural studies of such complexes as it does not require crystallization, uses far less sample, and is much faster. But for helical polymers most can never be crystallized and cryo-EM is not only the preferred method but the only method available for reaching near-atomic resolution. I will describe our most recent applications of cryo-EM to a range of systems, from viruses that infect organisms living in nearly boiling acid (1-3), to an archaeal pilus that is nearly indestructible (4), to “microbial nanowires” that conduct electrons (5). All of these studies provide not only new understanding of biology and evolution, but yield insights into novel structures that can have applications to drug delivery, biomedical engineering and nanotechnology.
- Liu Y, Osinski T, Wang F, Krupovic M, Schouten S, Kasson P, Prangishvili D, & Egelman EH (2018) Structural conservation in a membrane-enveloped filamentous virus infecting a hyperthermophilic acidophile. Nature communications 9(1):3360.
- Kasson P, DiMaio F, Yu X, Lucas-Staat S, Krupovic M, Schouten S, Prangishvili D, & Egelman EH (2017) Model for a novel membrane envelope in a filamentous hyperthermophilic virus. eLife 6:doi:10.7554/eLife.26268.
- DiMaio F, Yu X, Rensen E, Krupovic M, Prangishvili D, & Egelman EH (2015) A Virus that Infects a Hyperthermophile Encapsidates A-Form DNA. Science 348:914-917.
- Wang F, et al. (2019) An extensively glycosylated archaeal pilus survives extreme conditions. Nat Microbiol 4(8):1401-1410.
- Wang F, et al. (2019) Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over Micrometers. Cell 177(2):361-369.e310.