Katie Kaus, a PhD candidate in molecular biology and biochemistry, spoke on “Molecular Detectives: Investigating Protein Structure using X-ray Crystallography” during the Graduate Student Speaker Series March 26 in Exley Science Center.
The molecular structure of proteins is an important component in studying how proteins interact with each other, providing information about how cellular processes are carried out by specific proteins, Kaus explained. By studying the structure of specific proteins, scientists can understand why germs make us sick.
Kaus focused her presentation on members of a family of proteins called bacterial pore forming toxins (PFTs)–specifically Vibrio cholerae cytolysin (VCC) and Vibrio vulnificus hemolysin (VVH). These proteins are secreted by pathogenic strains of the aquatic bacteria, V. cholerae and V. vulnificus. V. cholerae is the human pathogen that causes cholera, an endemic disease in several parts of the world. V. vulnificus is found in contaminated seafood, such as raw oysters, as well as contaminated seawater. V. vulnificus most frequently causes gastrointestinal distress but can also cross from the gut into the blood stream resulting in lethal septicemia.
KVCC and VVH are homologous proteins that are secreted by their respective bacteria, bind to macromolecules at the surface of host cells, and undergo structural changes creating lytic pores in the host cell membrane. As part of her research, Kaus is interested in understanding how these bacterial proteins recognize and specifically attack human cells. Guided by biochemical assays, Kaus used a technique called X-ray crystallography to identify structural relationships between VCC or VVH and the biomolecules each protein binds.
X-ray crystallography involves obtaining protein molecules in a crystalline form and taking advantage of the manner in which an Xray beam is diffracted by the atoms that make up these protein crystals, to determine their arrangement within the 3-D space of a protein molecule. Pictured, Kaus looks at crystals under a microscope in Hall-Atwater Laboratory.
By using this approach, Kaus identified similar, yet distinct molecular mechanisms employed by VCC and VVH to specifically recognize and attack host cell membranes. Understanding how these proteins specifically attack human cells will aid in developing treatments against V. cholerae and V. vulnificus infection. (Photos by Olivia Drake)