Friday, June 15, 2012
Scientists have devised a new way to see how proteins, tiny machines naturally built inside our bodies, assemble. The research could help fight diseases such as Alzheimer’s and Parkinson’s—caused by errors in assembly—or enable bioengineers to make new molecular machines, the researchers say. The study was published June 10 in the journal Nature Structural and Molecular Biology. “All creatures, from bacteria to humans, monitor and transform their environments using small protein nanomachines made of thousands of atoms,” explained the senior author of the study, Stephen Michnick of the University of Montreal department of biochemistry. “For example, in our sinuses, there are complex receptor proteins that are activated in the presence of different odor molecules. Some of those scents warn us of danger; others tell us that food is nearby.” Proteins are made of long chains of amino acids, which have evolved over millions of years to self-assemble extremely rapidly—often in thousandths of a second or less—into a working “nanomachine,” or molecular-scale machine. “One of the main challenges for biochemists is to understand how these linear chains assemble into their correct structure given an astronomically large number of other possible forms,” Michnick said. “To understand how a protein goes from a linear chain to a unique assembled structure, we need to capture snapshots of its shape at each stage of assembly,” said Alexis Vallée-Bélisle, a co-author of the study. “The problem is that each step exists for a fleetingly short time and no available technique enables us to obtain precise structural information on these states within such a small time frame. We developed a strategy to monitor protein assembly by integrating fluorescent probes throughout the linear protein chain so that we could detect the structure of each stage of protein assembly, step by step to its final structure.” The assembly process, which begins using instructions in our DNA, is itself not the end of its journey. A protein can change, through chemical modifications or with age, to take on different forms and functions. “Understanding how a protein goes from being one thing to becoming another is the first step towards understanding and designing protein nanomachines for biotechnologies such as medical and environmental diagnostic sensors, drug synthesis or delivery,” Vallée-Bélisle said.