Our scientific presence evolves around the 3D visualization of protein nanomachines and the deconvolution of mechanistic aspects of their operation. This has been primarily accomplished through the application of molecular electron microscopy (cryo-EM and negative stain EM), currently the only technique that allows direct visualization of biological complexes at the molecular level.
Mancour LV, Daghestani HN, Dutta S, Westfield GH, Schilling J, Oleskie AN, Herbstman JF, Chou SZ, Skiniotis G. (2012). Ligand-induced architecture of the leptin receptor signaling complex. Mol Cell
Westfield GH, Rasmussen SG, Su M, Dutta S, DeVree BT, Chung KY, Calinski D, Velez-Ruiz G, Oleskie AN, Pardon E, Chae PS, Liu T, Li S, Woods VL Jr, Steyaert J, Kobilka BK, Sunahara RK, Skiniotis G. (2011). Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex. Proc Natl Acad Sci USA.
Leptin receptor structure
The Skiniotis lab obtained the first picture of the interaction between leptin and its receptor, illustrating how the receptor has two hinged legs that can swivel until they encounter leptin, which binds to the legs and makes them rigid. The leptin receptor is similar to other receptors in the same family, and the findings may provide insight into new targets for treatment of hormone-related diseases.
The work was published in Molecular Cell in October 2012.