Membrane protein ‘factory’ may lead to new drug treatments

Mastering proteins is a pathway to molecular nanotechnology. This is an advance towards understanding and mastering non-water soluable proteins.

PROTEIN FACTORY – Argonne biologists developed a membrane protein production “factory” using photosynthetic Rhodobacter, which can be engineered to express and incorporate the proteins into the cell’s cytoplasmic membrane, shown in white. Membrane proteins are difficult to study in traditional ways. Since they make up 60 percent of all drug targets, researchers are working to overcome the challenges.

Biologists at Argonne have engineered and patented a bacterial factory that enables the study of membrane proteins. These proteins are challenging to study, but critical to understand because they represent 60 percent of drug targets. Studies of membrane proteins could lead to new and improved pharmaceutical treatments for a broad range of illnesses such as depression, heart disease, addictions and cystic fibrosis.

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.

Laible and Hanson took advantage of the natural characteristics of the Rhodobacter species of photosynthetic bacteria they were working with in another project. Under certain conditions in response to light or oxygen Rhodobacter naturally produces large quantities of internal membranes.

The biologists developed a system that successfully expresses hundreds of copies of a chosen membrane protein in Rhodobacter while simultaneously synthesizing the internal membranes they want to live in.

So far the team has cloned about 500 genes into Rhodobacter. “First,” Laible said, “we produced a variety of membrane proteins of different sizes, functions and physical properties, and we have had a 60 percent success rate with them. Now we have cloned all of the membrane proteins of E. coli and are continuing production.”

As they continue to manufacture different membrane proteins, the team is tackling the next step to creating a pathway to protein crystallization for membrane proteins by developing specialized molecules, or reagents.