Parkinson Protein α-Synuclein Binds Surprisingly Strong with Membrane
Α-synuclein, a protein associated with Parkinson’s disease, proves to bind with membranes in a surprisingly efficient way. It confirms scientists’ suspicion of the protein’s leading role in the transmission of neurotransmitters between nerve cells in the brain. Publication in PLoS ONE.
Physicists of the universities of Leiden and Twente studied the binding process of α-synuclein with small vesicles. During the research, these played the part of specific vesicles which attach to the brain membrane and transfer neurotransmitters. First author Pravin Kumar and his colleagues used the Leiden developed method of keeping track of the binding process through electron spins.
Parksinson’s disease is the second most prevalent neurodegenerative disorder. Within the brain of a Parkinson patient, something goes wrong during the transport of neurotransmitters, which provide the communication between nerve cells. But it is still unknown when and where exactly the error occurs. However, scientist have already discovered that proteins accumulate in the brain, and α-synuclein is notably abundant there. The suspiciously dominant presence of this protein was cause for group leader Dr. Martina Huber to study its behavior.
Her group studied the binding of α-synuclein with vesicles, using their electron paramagnetische resonantie (EPR) technique. They placed several labels on the molecule, and by manipulating their electron spins they could keep track of the labels’ positions during the process. In this way, they monitored the behavior of the protein. They measured the mobility of the labels to determine which parts of the protein have maximum binding, and therefore move the least.
‘Much to my amazement it turns out that α-synuclein binds surprisingly well,’ says Huber. ‘Normally speaking, this kind of vesicles binds poorly because it is not very negatively charged. Still, we see this result.’ It provides a piece of the puzzle to figure out the cause of Parkinson’s disease. Huber: ‘The occurrence of a disease has many factors, including the truly malicious processes, but also correction mechanisms of the body that work correctly or fail. We need to map out all those pieces of the puzzle to see where exactly things take a turn for the worse. Now we see that α-synuclein plays an important role in Parkinson’s. You have a much better chance of finding a treatment once you understand how a disease works, so it is important that we came a step closer towards getting the full picture.’
Parkinson’s Protein α-Synuclein Binds Efficiently and with a Novel Conformation to Two Natural Membrane Mimics, Pravin Kumar, Ine M. J. Segers-Nolten, Nathalie Schilderink, Vinod Subramaniam, Martina Huber