Welcome to the Leiman Lab!
We study the structure and function of large dynamic macromolecular
complexes (biological nanomachines) comprised of hundreds of protein
molecules. Of particular interest are the bacterial type VI secretion
system (T6SS), R-type pyocins, and the host cell adsorption organelles
of bacterial viruses. These systems employ a rigid tube plus contractile
sheath mechanism for breaching the envelope of the target host cell and
are capable of translocating large proteins and DNA across lipid
We use a combination of X-ray crystallography and
electron microscopy with other biochemical and biophysical techniques.
Individual proteins and their complexes are crystallized and analyzed
using X-ray crystallography. The entire assembly is cryo-fixed and
imaged with a high-end electron microscope. These images are then used
to calculate a three-dimensional map of the entire assembly. The X-ray
atomic structures of the components can be placed into the electron
microscopy map, similar to a jigsaw puzzle, giving rise to a
pseudo-atomic resolution structure of the entire assembly. Such an
approach results in a tremendous amount of information and allows us to
understand the structure and function in atomic detail.