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 mainly working in two different areas: protein-DNA complexes active in homologous recombination and replication, and F-actin (Egelman, 2003). However, the development of new techniques in my lab to study RecA-DNA filaments and F-actin has led to new applications to such systems as bacterial Type Three Secretion Systems (Wang et al., 2006), filamentous bacteriophage and bacterial pili (Craig et al., 2006).

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. 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 are interested in how human Rad51 interacts with BRCA2, the protein product of a gene identified in familial breast cancer susceptibility (Galkin et al., 2005).

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 , which provides insight into many phenomena, including the ability of the cell to control how actin specifically binds more than 40 other proteins.

Selected References

Craig L, Volkmann N, Arvai AS, Pique ME, Yeager M, Egelman EH, Tainer JA. (2006) "Type IV pilus structure by cryo-electron microscopy and crystallography: implications for pilus assembly and functions." Mol Cell. Sep 23:651-62. [PubMed]

Ogawa T, Yu X, Shinohara A, Egelman EH. (1993) "Similarity of the yeast RAD51 filament to the bacterial RecA filament." Science. Mar 259(5103):1896-9. [PubMed]

Galkin VE, VanLoock MS, Orlova A, Egelman EH. (2002) "A new internal mode in F-actin helps explain the remarkable evolutionary conservation of actin's sequence and structure." Curr Biol. Apr 12:570-5. [PubMed]

Egelman EH. (2003) "A tale of two polymers: new insights into helical filaments." Nat Rev Mol Cell Biol. 4:621-30. [PubMed]

Galkin VE, Esashi F, Yu X, Yang S, West SC, Egelman EH. (2005) "BRCA2 BRC motifs bind RAD51-DNA filaments." Proc Natl Acad Sci U S A. Jun 102(24):8537-42. Epub 2005 Jun 3. [PubMed]

Orlova A, Garner EC, Galkin VE, Heuser J, Mullins RD, Egelman EH. (2007) "The structure of bacterial ParM filaments." Nat Struct Mol Biol. 14(10):921-6. Epub 2007 Sep 16. [PubMed]

Wang YA, Yu X, Yip C, Strynadka NC, Egelman EH. (2006) "Structural polymorphism in bacterial EspA filaments revealed by cryo-EM and an improved approach to helical reconstruction." Structure. 14:1189-96. [PubMed]