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 microscopy and computed image reconstruction. We have been working in two different areas: protein-DNA complexes active in homologous recombination and replication, and F-actin.

The E. coli RecA filament has been the most intensively studied enzyme in homologous recombination, and we have been studying the helical filament that the RecA filament forms on DNA which is the scaffold within which homologous recombination is initiated (Egelman, 1993). The RecA protein induces a highly unusual structure on the DNA within this filament, and this appears to be an important aspect of RecA's enzymatic role. We have shown that the eukaryotic homolog of RecA, the Rad51 protein, forms a nearly identical structure (Ogawa et al., 1993).

We have been looking at other protein-DNA complexes that act subsequent to RecA in catalyzing branch migration. This includes the RuvB protein (Yu et al., 1997), which is a member of a large superfamily of helicases. We are currently looking at other helicases, including E. coli DnaB, the bacteriophage T7 gp4, and the papilloma virus E1 proteins, which act in DNA replication.

Actin is the most ubiquitous and conserved eukaryotic protein. While it was first identified in muscle, as being the main component of the thin filaments, it is equally abundant in most non-muscle cells, where it plays a key role in the control of cell form and motility. We have found that the F-actin filament can exist in a number of different structural states (Belmont et al., 1999), which provides insight into many phenomena, including the ability of the cell to control how actin specifically binds more than 40 other proteins.

Selected Publications

  • 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
  • Galkin V, Britt R, Bane L, Yu X, Cox M, Egelman E. Two modes of binding of DinI to RecA filament provide a new insight into the regulation of SOS response by DinI protein. Journal of molecular biology. 2011;408(5): 815-24. PMID: 21458462 | PMCID: PMC3089025
  • 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
  • Reducing irreducible complexity: divergence of quaternary structure and function in macromolecular assemblies. Current opinion in cell biology. 2009;22(1): 68-74. PMID: 20006482
  • Egelman E, Amos L. Electron microscopy of helical filaments: rediscovering buried treasures in negative stain. BioEssays : news and reviews in molecular, cellular and developmental biology. 2009;31(9): 909-11. PMID: 19642111
  • 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
  • Esashi F, Galkin V, Yu X, Egelman E, West S. Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2. Nature structural & molecular biology. 2007;14(6): 468-74. PMID: 17515904
  • Reisler E, Egelman E. Actin structure and function: what we still do not understand. The Journal of biological chemistry. 2007;282(50): 36133-7. PMID: 17965017
  • 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
  • The iterative helical real space reconstruction method: surmounting the problems posed by real polymers. Journal of structural biology. 2006;157(1): 83-94. PMID: 16919474
  • Craig L, Volkmann N, Arvai A, Pique M, Yeager M, Egelman E, Tainer J. Type IV pilus structure by cryo-electron microscopy and crystallography: implications for pilus assembly and functions. Molecular cell. 2006;23(5): 651-62. PMID: 16949362
  • Galkin V, Orlova A, Fattoum A, Walsh M, Egelman E. The CH-domain of calponin does not determine the modes of calponin binding to F-actin. Journal of molecular biology. 2006;359(2): 478-85. PMID: 16626733
  • Galkin V, Wu Y, Zhang X, Qian X, He Y, Yu X, Heyer W, Luo Y, Egelman E. The Rad51/RadA N-terminal domain activates nucleoprotein filament ATPase activity. Structure (London, England : 1993). 2006;14(6): 983-92. PMID: 16765891
  • Kudryashov D, Galkin V, Orlova A, Phan M, Egelman E, Reisler E. Cofilin cross-bridges adjacent actin protomers and replaces part of the longitudinal F-actin interface. Journal of molecular biology. 2006;358(3): 785-97. PMID: 16530787