Welcome to the Leiman Lab!

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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 membranes.

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.