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

Galkin VE, Orlova A, Schroder GF, Egelman EH. (2010) "Structural polymorphism in F-actin." Nat Struct Mol Biol. 17(11):1318-23. Epub 2010 Oct 10. [PubMed]

Galkin VE, Orlova A, Salmazo A, Djinovic-Carugo K, Egelman EH. (2010) "Opening of tandem calponin homology domains regulates their affinity for F-actin." Nat Struct Mol Biol. 17:614-6. Epub 2010 Apr 11. [PubMed]

Hui MP, Galkin VE, Yu X, Stasiak AZ, Stasiak A, Waldor MK, Egelman EH. (2010) "ParA2, a Vibrio cholerae chromosome partitioning protein, forms left-handed helical filaments on DNA." Proc Natl Acad Sci U S A. Mar 107(10):4590-5. Epub 2010 Feb 22. [PubMed]

Egelman EH. (2010) "Reducing irreducible complexity: divergence of quaternary structure and function in macromolecular assemblies." Curr Opin Cell Biol. 22:68-74. Epub 2009 Dec 16. [PubMed]

Galkin VE, Orlova A, Rivera C, Mullins RD, Egelman EH. (2009) "Structural polymorphism of the ParM filament and dynamic instability." Structure. Sep 17:1253-64. [PubMed]

Galkin VE, Yu X, Bielnicki J, Heuser J, Ewing CP, Guerry P, Egelman EH. (2008) "Divergence of quaternary structures among bacterial flagellar filaments." Science. Apr 320(5874):382-5. [PubMed]