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A507 Richards Bldg |
Structure Biology of the Actin Cytoskeleton The actin cytoskeleton plays an essential role in multiple cellular functions, including cytokinesis, vesicular trafficking and the maintenance of cell shape and polarity. The driving force for these processes is the dynamic remodeling of the actin cytoskeleton into supramolecular functional networks. Remodeling of the cytoskeleton is a tightly regulated process, which involves hundreds of actin-binding and signaling proteins. The main focus of the research in our lab is to understand the molecular basis for how protein-protein interaction networks bring together cytoskeleton scaffolding, nucleation, elongation, and signaling proteins to accomplish specific cellular functions. Another area of significant interest is the study of large multi-domain proteins that connect the actin cytoskeleton to the cell membrane, and sense or induce membrane curvature. Our primary research tool is protein X-ray crystallography. The atomic snapshots resulting from crystal structures provide a wealth of knowledge, but lack information about the dynamic aspects of protein-protein interaction. To obtain this kind of information we also use a host of other approaches, including mutagenesis, bio-informatics, and biophysical methods such as isothermal titration calorimetry (ITC), multi-angle light scattering (MALS), small and wide angle X-ray scattering (SAXS/WAXS). The lab collaborates with cell biologists and electron microscopists to study actin cytoskeletal proteins in the cellular environtment. Selected Publications: Chereau D., Boczkowska M., Skwarek-Maruszewska A., Fujiwara I., Hayes D.B., Rebowski G., Lappalainen P., Pollard T.D. & Dominguez R. (2008) Leiomodin is an actin filament nucleator in muscle cells. Science 320:239-243. Boczkowska M., Rebowski G., Petoukhov M.V., Hayes D.B., Svergun D.I. & Dominguez R. (2008) X-ray scattering study of activated Arp2/3 complex with bound actin-WCA. Structure [in press] Lee S.H., Weins A., Hayes D.B., Pollak M.R. & Dominguez R. (2008) Crystal structure of the actin-binding domain of α-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis. J. Mol. Biol. 376:317-324. Ferron F., Rebowski G., Lee S.H. & Dominguez R. (2007) Structural basis for the recruitment of profilin–actin complexes during filament elongation by Ena/VASP. EMBO J. 26:4597-4606. Lee S.H., Hayes D.B., Rebowski G., Tardieux I., Dominguez R. (2007) Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer. PNAS 104:16122-16127. Dominguez R. (2007) The β-Thymosin/WH2 Fold: Multifunctionality and Structure. Ann N Y Acad Sci. 1112:86-94. Lee S.H., Kerff F., Chereau D., Ferron F., Klug A., Dominguez R. (2007) Structural basis for the actin-binding function of Missing-in-Metastasis. Structure 15:145-55. |
