Petr G. Leiman, PhD
Associate Professor, Department of Biochemistry & Molecular Biology
Tel: (409) 747-2078
Campus Location: 5.104B Basic Science Bldg
Mail Route: 0647
Lab Web Page
Our ultimate research goal is to describe how large dynamic
macromolecular complexes (biological nanomachines) work in quantitative
terms. Understanding the structure of these machines in atomic detail is
key to achieving this goal.
We use a combination of X-ray crystallography and electron microscopy
with other biochemical and biophysical techniques. The following systems
are of interest from the basic, fundamental science side or because of
their importance in technological or medicinal applications.
Bacterial type VI secretion system (T6SS)
Bacteria use secretion system to deliver complex substrates -
large toxins and enzymes, which alter cellular functions - in the
external milieu and sometimes directly into the cytoplasm or periplams
of target host cells. Seven distinct types of secretion systems (type I
through VII), have been characterized today. Compared to types I through
V, relatively little is known about the function and structure of the
type VI secretion system (T6SS). Despite being defined as a secretion
system very recently, the T6SS cluster of genes is present in more than
25% of all known bacterial genomes making T6SS one of the most
widespread secretion systems. T6SS appears to be a sole determinant of
pathogenicity of many bacterial strains. T6SS proteins assemble into a
large tubular structure spanning the cytoplasm and the envelope of the
cell. Several T6SS proteins are structurally and functionally related to
those found in contractile tails of bacteriophages. The tail is a
complex organelle, responsible for host recognition, penetration through
the multilayered host envelope, and delivery of phage DNA and proteins
from the phage capsid into the cytoplasm. The accumulated data suggest
that a similar protein complex is assembled by the T6SS proteins.
In addition to secretion systems, some bacteria use various
bacteriocins to suppress growth of other cells occupying the same niche.
Many strains of the widespread pathogen, Pseudomonas aeruginosa, can
produce pyocins, very potent bacteriocins, which are formed by one or
several protein molecules. The R-type pyocins are homologs of
contractile phage tails and, in turn, are related to the T6SS machine.
The pyocins represent a very potent proteinatious bactericidal, which
can be retargeted to a new host. These features make the R-type pyocins a
prospective lead as a therapeutical antimicrobial. Our aim is to
understand how R-type pyocins function at the atomic level of detail.
We study the structure and functional mechanism of host adsorption organelles of certain complex bacteriophages.