Edward H. Egelman

Education

  • BA, Brandeis University, Waltham, MA
  • PhD, Brandeis University, Waltham, MA
  • Postdoc, MRC Lab. of Mol. Biology, Cambridge, UK

Primary Appointment

  • Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Structure and Function of Macromolecular Complexes Using Electron Microscopy

Research Description

Our research is focused on the structure and function of macromolecular assemblies, using the techniques of electron cryo-microscopy and three-dimensional reconstruction. Historically, we have been working in two different areas: protein-DNA complexes and F-actin. However, the development of new techniques by us for working with helical polymers has expanded our interest to many other systems, from bacterial pili to the filaments formed on foreign RNA and DNA in the cell as part of the innate immune response. We are now at the point where we can achieve near-atomic resolution almost routinely for many filamentous biological assemblies!

A number of themes have emerged from our work. One is the lability of quaternary structure: while the overall fold of a protein is usually not altered by a small number of sequence changes, the higher-order assemblies formed by proteins can be dramatically changed. We have postulated that this provides an amplification of small sequence changes over the course of evolution, leading to increased divergence in structure and function. We have shown that this is true in the bacterial flagellar system, where very conserved subunits can assemble in different ways after small sequence changes.

On the other hand, we have been interested in why the sequence of actin has never changed (at least for the skeletal muscle isoform) over more than 350 million years of evolution: humans and chickens have identical sequences for this protein. Actin is the most ubiquitous and conserved eukaryotic protein, so the anomalous sequence conservation raises many questions. We have suggested that this intense selective pressure on every residue is due to extensive allosteric networks within the actin subunit that give the actin filament remarkable properties of cooperativity and the ability to exist in multiple structural states.

Selected Publications

  • Cryo-EM of bacterial pili and archaeal flagellar filaments. Current opinion in structural biology. 2017;46 31-37. PMID: 28609682
  • Frenz B, Walls A, Egelman E, Veesler D, DiMaio F. RosettaES: a sampling strategy enabling automated interpretation of difficult cryo-EM maps. Nature methods. 2017;14(8): 797-800. PMID: 28628127
  • Kasson P, DiMaio F, Yu X, Lucas-Staat S, Krupovic M, Schouten S, Prangishvili D, Egelman E. Model for a novel membrane envelope in a filamentous hyperthermophilic virus. eLife. 2017;6. PMID: 28639939 | PMCID: PMC5517147
  • López-Castilla A, Thomassin J, Bardiaux B, Zheng W, Nivaskumar M, Yu X, Nilges M, Egelman E, Izadi-Pruneyre N, Francetic O. Structure of the calcium-dependent type 2 secretion pseudopilus. Nature microbiology. 2017. PMID: 28993624
  • Ve T, Vajjhala P, Hedger A, Croll T, DiMaio F, Horsefield S, Yu X, Lavrencic P, Hassan Z, Morgan G, Mansell A, Mobli M, O'Carroll A, Chauvin B, Gambin Y, Sierecki E, Landsberg M, Stacey K, Egelman E, Kobe B. Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. Nature structural & molecular biology. 2017;24(9): 743-751. PMID: 28759049
  • Wang F, Coureuil M, Osinski T, Orlova A, Altindal T, Gesbert G, Nassif X, Egelman E, Craig L. Cryoelectron Microscopy Reconstructions of the Pseudomonas aeruginosa and Neisseria gonorrhoeae Type IV Pili at Sub-nanometer Resolution. Structure (London, England : 1993). 2017;25(9): 1423-1435.e4. PMID: 28877506
  • Zheng W, Wang F, Taylor N, Guerrero-Ferreira R, Leiman P, Egelman E. Refined Cryo-EM Structure of the T4 Tail Tube: Exploring the Lowest Dose Limit. Structure (London, England : 1993). 2017;25(9): 1436-1441.e2. PMID: 28757144 | PMCID: PMC5587399
  • The Current Revolution in Cryo-EM. Biophysical journal. 2016;110(5): 1008-12. PMID: 26958874 | PMCID: PMC4788751
  • Braun T, Vos M, Kalisman N, Sherman N, Rachel R, Wirth R, Schröder G, Egelman E. Archaeal flagellin combines a bacterial type IV pilin domain with an Ig-like domain. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(37): 10352-7. PMID: 27578865 | PMCID: PMC5027424
  • Costa T, Ilangovan A, Ukleja M, Redzej A, Santini J, Smith T, Egelman E, Waksman G. Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric Protein-Phospholipid Complex. Cell. 2016;166(6): 1436-1444.e10. PMID: 27610568 | PMCID: PMC5018250
  • Fu T, Li Y, Lu A, Li Z, Vajjhala P, Cruz A, Srivastava D, DiMaio F, Penczek P, Siegel R, Stacey K, Egelman E, Wu H. Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex. Molecular cell. 2016;64(2): 236-250. PMID: 27746017 | PMCID: PMC5089849
  • Hospenthal M, Redzej A, Dodson K, Ukleja M, Frenz B, Rodrigues C, Hultgren S, DiMaio F, Egelman E, Waksman G. Structure of a Chaperone-Usher Pilus Reveals the Molecular Basis of Rod Uncoiling. Cell. 2016;164(1): 269-78. PMID: 26724865 | PMCID: PMC4715182
  • Kolappan S, Coureuil M, Yu X, Nassif X, Egelman E, Craig L. Structure of the Neisseria meningitidis Type IV pilus. Nature communications. 2016;7 13015. PMID: 27698424 | PMCID: PMC5059446
  • Postel S, Deredge D, Bonsor D, Yu X, Diederichs K, Helmsing S, Vromen A, Friedler A, Hust M, Egelman E, Beckett D, Wintrode P, Sundberg E. Bacterial flagellar capping proteins adopt diverse oligomeric states. eLife. 2016;5. PMID: 27664419 | PMCID: PMC5072837
  • Subramaniam S, Earl L, Falconieri V, Milne J, Egelman E. Resolution advances in cryo-EM enable application to drug discovery. Current opinion in structural biology. 2016;41 194-202. PMID: 27552081 | PMCID: PMC5154827
  • DiMaio F, Chen C, Yu X, Frenz B, Hsu Y, Lin N, Egelman E. The molecular basis for flexibility in the flexible filamentous plant viruses. Nature structural & molecular biology. 2015;22(8): 642-4. PMID: 26167882 | PMCID: PMC4527879
  • DiMaio F, Yu X, Rensen E, Krupovic M, Prangishvili D, Egelman E. Virology. A virus that infects a hyperthermophile encapsidates A-form DNA. Science (New York, N.Y.). 2015;348(6237): 914-7. PMID: 25999507 | PMCID: PMC5512286
  • Egelman E, Xu C, DiMaio F, Magnotti E, Modlin C, Yu X, Wright E, Baker D, Conticello V. Structural plasticity of helical nanotubes based on coiled-coil assemblies. Structure (London, England : 1993). 2015;23(2): 280-9. PMID: 25620001 | PMCID: PMC4318749
  • Kudryashev M, Wang R, Brackmann M, Scherer S, Maier T, Baker D, DiMaio F, Stahlberg H, Egelman E, Basler M. Structure of the type VI secretion system contractile sheath. Cell. 2015;160(5): 952-62. PMID: 25723169 | PMCID: PMC4359589
  • Lu A, Magupalli V, Ruan J, Yin Q, Atianand M, Vos M, Schröder G, Fitzgerald K, Wu H, Egelman E. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell. 2014;156(6): 1193-206. PMID: 24630722 | PMCID: PMC4000066
  • Berke I, Yu X, Modis Y, Egelman E. MDA5 assembles into a polar helical filament on dsRNA. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(45): 18437-41. PMID: 23090998 | PMCID: PMC3494895
  • Galkin V, Orlova A, Egelman E. Actin filaments as tension sensors. Current biology : CB. 2012;22(3): R96-101. PMID: 22321312 | PMCID: PMC3277726
  • Galkin V, Orlova A, Kudryashov D, Solodukhin A, Reisler E, Schröder G, Egelman E. Remodeling of actin filaments by ADF/cofilin proteins. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(51): 20568-72. PMID: 22158895 | PMCID: PMC3251117
  • Galkin V, Orlova A, Schröder G, Egelman E. Structural polymorphism in F-actin. Nature structural & molecular biology. 2010;17(11): 1318-23. PMID: 20935633 | PMCID: PMC2988880
  • Galkin V, Orlova A, Rivera C, Mullins R, Egelman E. Structural polymorphism of the ParM filament and dynamic instability. Structure (London, England : 1993). 2009;17(9): 1253-64. PMID: 19748346 | PMCID: PMC2745721
  • Frost A, Perera R, Roux A, Spasov K, Destaing O, Egelman E, De Camilli P, Unger V. Structural basis of membrane invagination by F-BAR domains. Cell. 2008;132(5): 807-17. PMID: 18329367 | PMCID: PMC2384079
  • Galkin V, Orlova A, Cherepanova O, Lebart M, Egelman E. High-resolution cryo-EM structure of the F-actin-fimbrin/plastin ABD2 complex. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(5): 1494-8. PMID: 18234857 | PMCID: PMC2234172
  • Single-particle reconstruction from EM images of helical filaments. Current opinion in structural biology. 2007;17(5): 556-61. PMID: 17851070 | PMCID: PMC2443787