- Biomedical Sciences Graduate Program | Edward H. Egelman

Edward H. Egelman


  • 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


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

  • 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
  • Pang X, Fan J, Zhang Y, Zhang K, Gao B, Ma J, Li J, Deng Y, Zhou Q, Egelman E, Hsu V, Sun F. A PH Domain in ACAP1 Possesses Key Features of the BAR Domain in Promoting Membrane Curvature. Developmental cell. 2014;31(1): 73-86. PMID: 25284369 | PMCID: PMC4198613
  • Wu B, Peisley A, Tetrault D, Li Z, Egelman E, Magor K, Walz T, Penczek P, Hur S. Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I. Molecular cell. 2014;55(4): 511-23. PMID: 25018021 | PMCID: PMC4142144
  • Qiao Q, Yang C, Zheng C, Fontán L, David L, Yu X, Bracken C, Rosen M, Melnick A, Egelman E, Wu H. Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Molecular cell. 2013;51(6): 766-79. PMID: 24074955 | PMCID: PMC3929958
  • 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, Egelman E. Are ParM Filaments Polar or Bipolar? Journal of molecular biology. 2012;423(4): 482-5. PMID: 22922064 | PMCID: PMC3467344
  • Yu X, Goforth C, Meyer C, Rachel R, Wirth R, Schröder G, Egelman E. Filaments from Ignicoccus hospitalis show diversity of packing in proteins containing N-terminal type IV pilin helices. Journal of molecular biology. 2012;422(2): 274-81. PMID: 22659006 | PMCID: PMC3599786
  • 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
  • Orlova A, Galkin V, Jeffries C, Egelman E, Trewhella J. The N-terminal domains of myosin binding protein C can bind polymorphically to F-actin. Journal of molecular biology. 2011;412(3): 379-86. PMID: 21821050 | PMCID: PMC3167005
  • Implications of the RecA structure. F1000 biology reports. 2010;1 7. PMID: 20948618 | PMCID: PMC2920672
  • 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
  • Grintsevich E, Galkin V, Orlova A, Ytterberg A, Mikati M, Kudryashov D, Loo J, Egelman E, Reisler E. Mapping of drebrin binding site on F-actin. Journal of molecular biology. 2010;398(4): 542-54. PMID: 20347847 | PMCID: PMC2866048
  • Yu X, Egelman E. Helical filaments of human Dmc1 protein on single-stranded DNA: a cautionary tale. Journal of molecular biology. 2010;401(3): 544-51. PMID: 20600108 | PMCID: PMC2917623
  • Problems in fitting high resolution structures into electron microscopic reconstructions. HFSP journal. 2009;2(6): 324-31. PMID: 19436497 | PMCID: PMC2645587
  • 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
  • Lucarelli D, Wang Y, Galkin V, Yu X, Wigley D, Egelman E. The RecB nuclease domain binds to RecA-DNA filaments: implications for filament loading. Journal of molecular biology. 2009;391(2): 269-74. PMID: 19540850 | PMCID: PMC2749006
  • Makhov A, Sen A, Yu X, Simon M, Griffith J, Egelman E. The bipolar filaments formed by herpes simplex virus type 1 SSB/recombination protein (ICP8) suggest a mechanism for DNA annealing. Journal of molecular biology. 2009;386(2): 273-9. PMID: 19138689 | PMCID: PMC2757162
  • 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, Brieher W, Kueh H, Mitchison T, Egelman E. Coronin-1A stabilizes F-actin by bridging adjacent actin protomers and stapling opposite strands of the actin filament. Journal of molecular biology. 2008;376(3): 607-13. PMID: 18177666 | PMCID: PMC2267021
  • 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
  • Huang R, Wang Y, Roth R, Yu X, Purvis A, Heuser J, Egelman E, Sadler J. Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(2): 482-7. PMID: 18182488 | PMCID: PMC2206562
  • Zhang X, Galkin V, Yu X, Egelman E, Heyer W. Loop 2 in Saccharomyces cerevisiae Rad51 protein regulates filament formation and ATPase activity. Nucleic acids research. 2008;37(1): 158-71. PMID: 19033358 | PMCID: PMC2615628
  • Single-particle reconstruction from EM images of helical filaments. Current opinion in structural biology. 2007;17(5): 556-61. PMID: 17851070 | PMCID: PMC2443787
  • Bugreev D, Yu X, Egelman E, Mazin A. Novel pro- and anti-recombination activities of the Bloom's syndrome helicase. Genes & development. 2007;21(23): 3085-94. PMID: 18003860 | PMCID: PMC2081975
  • Shvetsov A, Galkin V, Orlova A, Phillips M, Bergeron S, Rubenstein P, Egelman E, Reisler E. Actin hydrophobic loop 262-274 and filament nucleation and elongation. Journal of molecular biology. 2007;375(3): 793-801. PMID: 18037437 | PMCID: NIHMS38812