Protein factory could lead to new drug treatments
drug targets could lead to new and improved pharmaceutical
treatments for a broad range of illnesses such as depression, heart
disease, addictions and cystic fibrosis.
Researchers believe that the factory has cut time and costs in automating the many steps it takes to determine the 3D structures of proteins and as a result the structures of thousands of proteins are now known.
The biologists from >Argonne National Laboratory, developed a system that expresses hundreds of copies of a chosen membrane protein in Rhodobacter, a species of photosynthetic bacteria, while simultaneously synthesising the internal membranes they want to live in.
The team has cloned approximately 500 genes into Rhodobacter as they first produced a variety of membrane proteins of different sizes, functions and physical properties.
"We have had a 60 per cent success rate with them. Now we have cloned all of the membrane proteins of E. coli and are continuing production," said Argonne biophysicist Phil Laible.
Biologists use three-dimensional images of proteins to better understand how proteins work. In drug design, the 3-D images help researchers develop a drug that specifically blocks binding of a biological attacker that would cause disease.
The biologists aim to focus on the designer detergents that remove the membrane protein from the lipid bi-layer where it resides, as well as antibodies to stabilise the membrane protein.
Additionally, they will keep an eye on the molecules that mimic the lipid bi-layer, or membrane.
Membrane proteins perform essential processes in the cell, such as controlling the flow of information and materials between cells and mediating activities like nerve impulses and hormone action.
These proteins are located in the rugged, oily two-layered membrane that holds the cell together. One-third of the genome of any organism encodes membrane proteins.
"When a cell is attacked by a virus or a bacterium, primary entry into the cell is via an association with proteins in the cell membrane," said Laible.
"In addition, in many disease states, the essential processes controlled by membrane proteins go awry. That is why so many membrane proteins are drug targets."
Researchers studying water-soluble proteins often use commercial E. coli -based systems to express, or produce, copies of the protein.
When membrane proteins are produced in E. coli, they overload the cell's bi-layers and cause the cells to die.
The sources that have yielded the majority of the few known membrane-protein structures are organisms in which the target membrane protein is naturally abundant.
