Edward H. Egelman
Professor of Biochemistry & Molecular Genetics
Ph.D., Brandeis University
Structure and Function in Macromolecular Assemblies

Laboratory
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Our research is focused on the structure and function of macromolecular assemblies, using the techniques of electron microscopy and computed image reconstruction. In the past we mainly worked 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).

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 100 other proteins. It has only become clear in the past ten years that actin has prokaryotic homologs involved in a large range of different activities. Our studies of one of these homologs, ParM, has given us new insights into how quaternary, or higher order, structure can diverge much more rapidly than tertiary structure, which is the fold of a protein. Thus, many proteins that share the same fold can assemble into very different filaments or assemblies, and these can have many different functions that are not simply dictated by the fold of the protein. We have shown the same thing with regards to a homolog of bacterial Type IV pilin being used in archaea to form very different filaments (Yu et al., 2012).


Selected References

Berke IC, Yu X, Modis Y, Egelman EH. (2012) "MDA5 assembles into a polar helical filament on dsRNA." Proc Natl Acad Sci U S A. Nov 109(45):18437-41. doi:10.1073/pnas.1212186109. Epub 2012 Oct 22. [PubMed]

Galkin VE, Orlova A, Egelman EH. (2012) "Actin filaments as tension sensors." Curr Biol. Feb 22:R96-101. doi: 10.1016/j.cub.2011.12.010. [PubMed]

Galkin VE, Orlova A, Kudryashov DS, Solodukhin A, Reisler E, Schröder GF, EgelmanEH. (2011) "Remodeling of actin filaments by ADF/cofilin proteins." Proc Natl Acad Sci U S A. Dec 108(51):20568-72. doi:10.1073/pnas.1110109108. Epub 2011 Dec 7. [PubMed]

Galkin VE, Orlova A, Schröder GF, Egelman EH. (2010) "Structural polymorphism in F-actin." Nat Struct Mol Biol. 17(11):1318-23. doi: 10.1038/nsmb.1930. Epub 2010Oct 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. doi: 10.1038/nsmb.1789. 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. doi:10.1073/pnas.0913060107. Epub 2010 Feb 22. [PubMed]