Scientists at the University of Montreal have developed a new approach to visualize how proteins assemble.
According to Professor Stephen Michnick, the research is expected to help bioengineers design new molecular machines for nanotechnology applications, as well as significantly aid our understanding of diseases such as Alzheimer’s and Parkinson’s, both of which are caused by errors in assembly.
“In order to survive, all creatures, from bacteria to humans, monitor and transform their environments using small protein nanomachines made of thousands of atoms,” explained Michnick.
“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.”
Indeed, proteins are made of long linear chains of amino acids, which have evolved over millions of years to self-assemble extremely rapidly – often within thousandths of a split second – into a working nanomachine.
“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.
Researcher Dr. Alexis Vallée-Bélisle expressed similar sentiments.
“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,” Vallée-Bélisle noted.
“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.”
However, Vallée-Bélisle emphasized that the protein assembly process “is not the end of its journey,” as a protein can change, via 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 of delivery,” he added.